BR112020010216A2 - dopamine ¿hydroxylase inhibitors - Google Patents

Abstract

This invention relates to: (a) compounds of formula Ia (with R1, R4 to R6, n and A as defined herein) and their pharmaceutically acceptable salts or solvates which are useful as dopamine-ß-hydroxylase inhibitors; (b) pharmaceutical compositions comprising such compounds, salts or solvates; (c) the use of such compounds, salts or solvates in therapy; (d) therapeutic methods of treatment using such compounds, salts or solvates; and (e) processes and intermediates useful for the synthesis of such compounds.

Description

"DOPAMINE-Β-HYDROXYLASE INHIBITORS". FIELD OF THE INVENTION

[001] This invention relates to: (a) compounds and their pharmaceutically acceptable salts or solvates which are useful as dopamine-β-hydroxylase inhibitors; (b) pharmaceutical compositions comprising such compounds, salts or solvates; (c) the use of such compounds, salts or solvates in therapy; and (d) therapeutic methods of treatment using such compounds, salts or solvates.

BACKGROUND OF THE INVENTION

[002] The enzyme dopamine-β-hydroxylase (DβH), also known as dopamine β-monooxygenase, is expressed in the peripheral and central nervous system (CNS). DβH catalyzes specific dopamine hydroxylation (DA) to produce norepinephrine, also known as norepinephrine (NA). As such, DβH inhibitors can inhibit NA biosynthesis, limiting its concentration and increasing AD levels.

[003] In recent years, interest in the development of DβH inhibitors has centered on the hypothesis that inhibition of this enzyme can provide significant clinical improvements in patients suffering from cardiovascular disorders, such as hypertension or chronic heart failure. The justification for the use of DβH inhibitors is based on their ability to inhibit NA biosynthesis, which is achieved through enzymatic hydroxylation of DA. The reduction of NA biosynthesis through DβH inhibition can directly dampen the function of the sympathetic nerve, the activation of which is the main clinical manifestation of congestive heart failure (Parmley, WW, Clin. Cardiol., 18: 440-445, 1995). Patients with congestive heart failure have elevated plasma noradrenaline concentrations (Levine, T.B. et al., Am. J. Cardiol., 49: 1659-1666, 1982), increased central sympathetic discharge (Leimbach, W.N.

et al., Circulation, 73: 913-919, 1986) and increased cardiorrenal noradrenaline leakage (Hasking, G.J. et al., Circulation, 73: 615-621, 1966). Prolonged and excessive myocardial exposure to noradrenaline can lead to negative regulation of cardiac β1-adrenoceptors, left ventricular remodeling, arrhythmias and necrosis, all of which can decrease the functional integrity of the heart. Patients with congestive heart failure who have high concentrations of noradrenaline in plasma also have the most adverse long-term prognosis (Cohn, J.N. et al., N. Engl. J. Med., 311: 819-823, 1984). Of greater significance is the observation that plasma norepinephrine concentrations are already high in asymptomatic patients without evident heart failure and can predict future mortality and morbidity (Benedict, C.R. et al., Circulation, 94: 690-697, 1996). An activated sympathetic impulse is thus not merely a clinical marker of congestive heart failure, but it can contribute to the progressive worsening of the disease.

[004] DβH inhibitors may also show activity in the CNS, if they cross the blood-brain barrier (BBB).

[005] Several DβH inhibitors have thus far been reported in the literature. The initial first and second generation examples, such as disulfiram (Goldstein, M. et al., Life Sci., 3: 763, 1964) and diethyldithiocarbamate (Lippmann, W. et al., Biochem. Pharmacol. , 18: 2507, 1969) or fusaric acid (Hidaka, H. Nature, 231, 1971) and aromatic alkylthioureas or thioureas (Johnson, GA et al, J. Pharmacol. Exp. Ther., 171: 80, 1970) have low potency, showed poor selectivity for DβH and caused toxic side effects. It was found that the third generation of DβH inhibitors, however, has much greater potency, such as, for example, nepicastat (RS-25560-197, IC50 9 nM) (Stanley, WC, et al., Br. J. Pharmacol., 121: 1803-1809, 1997), which was developed for initial clinical trials. Although it was initially developed for peripheral indications (hypertension and congestive heart failure), an important discovery was that nepicastat crosses the BBB, and was thus able to cause central as well as peripheral effects.

[006] Nepicastat and its analogs are disclosed in WO 95/29165. In addition, WO 2004/033447 and WO 2008/136695 disclose DβH inhibitors that have high potency and significantly reduced brain access, giving rise to potent and peripherally selective DβH inhibitors. However, these compounds are also difficult to synthesize, requiring many steps in the synthetic route, making them expensive to manufacture. In particular, the potent compounds disclosed in WO 2008/136695 are poorly soluble and have improved levels of exposure when administered with high-fat meals. A review of the mechanism, substrates and DβH inhibitors is given by Beliaev, A., et al. in Current Enzyme Inhibition, 5, 27-43, 2009.

[007] WO2018 / 056854 and WO2018 / 056855 disclose DβH inhibitors that are useful for the treatment of conditions eased by DβH inhibition within the CNS. Compared to the compounds of formula Ia of the present invention, the compounds of WO2018 / 056854 and WO2018 / 056855 have different substituents at the R6 position. In addition, the subtitles for Step 3 of Example 80 of WO2018 / 056854 and Step 3 of Example 3 of WO2018 / 056855 incorrectly disclose the chemical name (S) -1-benzyl-6- (3,5-difluorophenyl ) -6,7-dihydro-2H-pyrrolo [1,2- c] imidazole-3 (5H) -thione instead of the real name of the compound (S) -1- butyl-6- (3,5- difluorophenyl) -6,7-dihydro-2H-pyrrolo [1,2-c] imidazole-3 (5H) - thiona (emphasis added).

[008] Thus, there remains an unmet clinical requirement for a potent, non-toxic and peripherally selective DβH inhibitor, which could be used for the treatment of certain cardiovascular disorders. A DβH inhibitor with similar or even greater potency than nepicastat, but lacking effects on the CNS (ie, unable to cross the BBB effectively), still having a long time on the periphery in order to provide a long duration of inhibition of DβH would provide a significant improvement over all DβH inhibitor compounds described thus far in the prior art. In addition, such compounds would preferably be orally bioavailable, highly soluble and easier and cheaper to synthesize.

SUMMARY OF THE INVENTION

[009] The present invention provides a compound of formula Ia, or a pharmaceutically acceptable salt or solvate thereof: wherein:

[0010] R1 is hydrogen, C1-C6 alkyl, partially or totally deuterated C1-C6 alkyl or C3-C6 cycloalkyl;

[0011] R4 is hydrogen or C1-C3 alkyl;

[0012] R5 is hydrogen;

[0013] or R4 and R5 combine, together with the carbon atoms to which they are attached, to form a cyclopropyl ring;

[0014] R6 is -COOH, -CHO, or - (CH2) m-X,

[0015] where:

[0016] m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with;

[0017] X is hydroxy, C1-C3 alkoxy, cyano, - N = CH (NHCN) (NH2), -NH-C (pyrrolidin-1-yl) = NCN, 5 or 6 membered heteroaryl optionally substituted with a group methyl, phenyl, -SO2- R7, -NR8R9,

[0018] -CO2R10, -CH (CO2R10) 2, -CONR11R12 or -NR13COR14;

[0019] where:

[0020] R7 is C1-C3 alkyl;

[0021] R8 is hydrogen or C1-C3 alkyl;

[0022] R9 is hydrogen,

[0023] C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl, phenyl, 5 or 6 membered heterocyclyl and 5 or 6 membered heteroaryl optionally substituted with a methyl substituent,

[0024] C3-C6 cycloalkyl,

[0025] heteroaryl with 5 or 6 members, or

[0026] 5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;

[0027] or R8 and R9 combine together with the N atom to which they are attached to form a

[0028] 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, starch, (N, N-dimethyl) acetamide and pyridyl or with one or two selected substituents fluoro and oxo, or a

[0029] heterospirocyclyl group with 9 or 10 members;

[0030] R10 is hydrogen or C1-C3 alkyl;

[0031] R11 is hydrogen or C1-C3 alkyl;

[0032] R12 is hydrogen,

[0033] C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of cyano, hydroxy, methylsulfonyl, C1-C2 alkoxy, dimethylamino, C3-C6 cycloalkyl, phenyl, 5 or 6 membered heteroaryl optionally substituted with a 5 or 6-membered methyl and heterocyclyl substituent optionally substituted with a t-Boc group or with one or two fluoro substituents,

[0034] C3-C6 cycloalkyl optionally substituted with a substituent selected from the group consisting of cyano, hydroxy, hydroxymethyl and oxo,

[0035] cyan,

[0036] methylsulfonyl,

[0037] CH2COO (C1-C3 alkyl),

[0038] heteroaryl with 5 or 6 members optionally substituted with a methyl substituent,

[0039] heterocyclyl with 4, 5 or 6 members optionally substituted with one or two substituents selected from oxo and methyl,

[0040] CH2CH (NH2) (COOH), or

[0041] CH (CH3) CONH2;

[0042] or R11 and R12 combine together with the N atom to which they are attached to form a

[0043] 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from monofluoromethyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, cyano, starch, (N, N-dimethyl) acetamide and pyridyl, or with one or two substituents selected from fluoro, methyl and oxo, or optionally fused with a cyclopropyl ring which can be substituted with one or two methyl substituents, or one

[0044] heterospirocyclyl group with 9 or 10 members;

[0045] R13 is hydrogen or C1-C3 alkyl;

[0046] R14 is C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl and phenyl,

[0047] C3-C6 cycloalkyl,

[0048] heteroaryl with 5 or 6 members, or

[0049] 5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;

[0050] A is C5-C7 cycloalkyl, furanyl, thiophenyl, methylthiophenyl or X1 X1 'X2 X2' X3, where:

[0051] X1 is hydrogen, halo or methyl;

[0052] X1 'is hydrogen or halo;

[0053] X2 is hydrogen, halo or methyl;

[0054] X2 'is hydrogen or halo;

[0055] X3 is hydrogen or fluoro;

[0056] n is 0 or 1, and when n is 0 a single bond is attached to the carbon atoms to which the CH2 unit would be attached when n is

1.

[0057] This invention is also directed to a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, for use in therapy.

[0058] This invention is also directed to a compound of formula

La, as defined above, or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of conditions ameliorated by inhibition of DβH outside the CNS.

[0059] This invention is also directed to a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of conditions alleviated by inhibition of DβH outside the CNS.

[0060] This invention is also directed to a method for treating or preventing conditions eased by inhibition of DβH outside the CNS comprising administering a therapeutically effective amount of a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, to a patient with his need.

This invention is also directed to a pharmaceutical composition comprising (i) a therapeutically effective amount of a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof; and (ii) a pharmaceutically acceptable excipient.

[0062] This invention is also directed to a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, with the proviso that the compound (S) -1-benzyl-6- (3,5- difluorophenyl) -6,7-dihydro-2H-pyrrolo [1,2-c] imidazole-3 (5H) -thione is excluded.

[0063] Certain compounds of formula Ia can exist as tautomers. As far as tautomers exist, each tautomeric form, and mixtures thereof, are contemplated as included in the present invention. Any reference in this description to a specific tautomer of a compound of formula Ia is understood to encompass each tautomeric form, as well as any mixtures thereof, for any reason. The same applies to tautomers of more specific modalities of the compounds of formula Ia described herein, such as, but not limited to, tautomers of compounds of formula Ib, Ic, Id, Ie, If, Ig, Ih, Ii and Ij described below , and tautomers of the specific examples described in the experimental section below.

DETAILED DESCRIPTION OF THE MODALITIES A. Definitions

[0064] "C1-C6 alkyl" means a saturated, unsubstituted, monovalent straight-chain or branched-chain hydrocarbon radical having from 1 to 6 carbon atoms. "C1-C2 alkyl", "C1-C3 alkyl", "C1-C4 alkyl" and "C1-C5 alkyl" have similar meanings.

[0065] "C1-C6 alkyl partially or totally deuterated" means C1-C6 alkyl in which some or all of the hydrogen atoms have been replaced by deuterium.

[0066] "C3-C6 cycloalkyl" means a cyclic, saturated, unsubstituted, monovalent hydrocarbon radical, having from 3 to 6 carbon atoms. "C5-C7 cycloalkyl" has an analogous meaning.

[0067] "C1-C3 alkoxy" means a monovalent, saturated, unsubstituted, straight chain or branched chain hydrocarbon having from 1 to 3 carbon atoms attached to the rest of the compound of formula Ia by means of a single oxygen atom. "C1-C2 alkoxy" has an analogous meaning.

[0068] "Heteroaryl with 5 or 6 members" means a monocyclic aromatic group with a total of 5 atoms in the ring where from 1 to 4 of these atoms are each independently selected from N, O and S; or a monocyclic aromatic group with a total of 6 ring atoms, where from 1 to 3 of these atoms are N. Heteroaryl groups with 5 members include pyrrolyl (also called azolyl), furanyl, thienyl (also called thiophenyl), pyrazolyl (also called 1H-pyrazolyl and 1,2-diazolyl), imidazolyl, oxazolyl (also called 1,3-oxazolyl), isoxazolyl (also called 1,2-oxazolyl), thiazolyl

(also called 1,3-thiazolyl), isothiazolyl (also called 1,2-thiazolyl), triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, oxatriazolyl and thiatriazolyl. 6-membered heteroaryl groups include dinylapyridinyl, pyrimidyl, pyrazinyl, pyridazinyl and triazinyl.

[0069] "Heterocyclyl with 4, 5 or 6 members" means a saturated monocyclic group with a total of 4 atoms in the ring where 1 of these atoms is selected from N, O and S; or a saturated monocyclic group with a total of 5 ring atoms where 1 or 2 of these atoms are each independently selected from N, O and S; or a saturated monocyclic group with a total of 6 ring atoms where 1 or 2 of these atoms are each independently selected from N, O and S. 4-membered heterocyclyl groups include azetidine, oxetane and tiethane. 5-membered heterocyclyl groups include pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl (also called tetrahydrothiophenyl), imidazolidinyl, pyrazolidinyl, dioxolanyl, dithiolanyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl and isothiazolidinyl. 6-membered heterocyclyl groups include piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperazinyl, dioxanyl, dithianyl, morpholinyl and thiomorpholinyl.

[0070] "5- or 6-membered N-heterocyclyl" means a saturated monocyclic group with a total of 5 atoms in the ring where 1 of these atoms is N and the other of these atoms is optionally selected from N, O and S; or a saturated monocyclic group with a total of 6 ring atoms where 1 of these atoms is N and another of these atoms is optionally independently selected from N, O and S. 5-membered N-heterocyclyl groups include pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl , isoxazolidinyl, thiazolidinyl and isothiazolidinyl. 6-membered N-heterocyclyl groups include piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl.

[0071] "Heterospirocyclyl with 9 or 10 members" means a saturated spirocyclic group with a total of 9 atoms in the two rings where from 1 to 4 of these atoms are each independently selected from N, O and S; or a saturated spirocyclic group with a total of 10 atoms in the two rings where from 1 to 5 of these atoms are each independently selected from N, O and S. 9-membered heterospirocyclic groups include 2-oxa-7- azospiro [4.4 ] nonanil. Heterospirocyclyl groups with 10 members include 2-oxa-8-azospiro [4.5] decanyl and 1,4-dioxa-8-azospiro [4.5] decanyl.

[0072] "oxo" means an oxo radical, and can be represented as = O.

[0073] "halo" means a fluorine radical (which can be represented as -F), chlorine (which can be represented as -Cl), bromine (which can be represented as -Br) or iodine (which can be represented as -I).

[0074] "starch" means -CONH2.

[0075] "t-Boc" means tert-butyloxycarbonyl.

[0076] "Pharmaceutically acceptable salt" means a salt such as those described in standard texts on salt formation, see, for example: P. Stahl, et al., Handbook of Pharmaceutical Salts: Properties, Selection and Use (VCHA / Wiley-VCH, 2002), or SM Berge, et al., "Pharmaceutical Salts" (1977) Journal of Pharmaceutical Sciences, 66, 1-19.

"Pharmaceutically acceptable solvate" means a molecular complex comprising the compound of the invention and one or more pharmaceutically acceptable solvent molecules, for example, water or ethanol. The term "hydrate" can be used when said solvent is water. Pharmaceutically acceptable solvates include hydrates and other solvates in which the crystallization solvent can be replaced isotopically, e.g. D2O, d6-acetone, d6-DMSO.

"Pharmaceutically acceptable excipient" means any ingredient other than the compound or compounds of the invention, or other known pharmacologically active components. The choice of excipient will depend largely on factors, such as the particular mode of administration, the effect of the excipient on solubility and stability, and the nature of the dosage form.

[0079] "Therapy", "treatment" and "treating" include the preventive and curative treatment of a condition, disease or disorder. It also includes slowing, stopping, controlling, or stopping the progression of a condition, disease, or disorder. It also includes preventing, curing, delaying, interrupting, controlling or stopping the symptoms of a condition, illness or disorder.

[0080] Other variations of the disclosed modalities can be understood and performed by those skilled in the art the practice of the claimed invention, from a study of the description, and the attached claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "one" or "one" does not exclude a plurality. The mere fact that certain measures are referred to in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. B. Compounds

The invention provides a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof: either D or D or D.

[0082] The invention also provides a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, with the proviso that the compound (S) -1-benzyl-6- (3,5-difluorophenyl) -6,7-dihydro-2H-pyrrolo [1,2-c] imidazole-3 (5H) -thione is excluded.

[0083] B0. Nuclear structures

[0084] In some embodiments of formula Ia, n is 0 and a single bond attaches to the carbon atoms to which the CH2 moiety would be attached when n is 1 to form a structure of formula Ib or D or D or D.

[0085] In some modalities of formula Ia, R4 and R5 combine, together with the carbon atom to which they are attached, to form a structure of formula Ic: either D or D or D.

[0086] In some embodiments more than 50%, preferably more than 90%, more preferably, more than 95% and even more preferably, more than 99% of the R5 and A substituents of the compounds of formula Ia have the stereochemical configuration of the formula Id or D or D or D.

[0087] In some embodiments more than 50%, preferably more than 90%, more preferably more than 95% and even more preferably, more than 99% of the R5 and A substituents of the compounds of formula Ia have the stereochemical configuration of formula Ie or D or D or D.

[0088] Preferred embodiments of formula Ia include compounds of formula If.

[0089] In some particularly preferred embodiments of the If formula more than 50%, preferably more than 90%, more preferably more than 95%, and even more preferably,

more than 99% of the R5 and A substituents of the compounds of formula If have the stereochemical configuration of the formula Ig.

[0090] In other more particularly preferred embodiments of If formula more than 50%, preferably more than 90%, more preferably more than 95% and even more preferably more than 99% of the substituents R5 and A of the compounds of formula If have the stereochemical configuration of formula Ih.

[0091] More preferred embodiments of formula Ia include compounds of formula Ii.

.

[0092] In some particularly preferred embodiments of formula Ii more than 50%, preferably more than 90%, more preferably more than 95% and even more preferably more than 99% have the stereochemical configuration of formula Ij.

. B1. Substituent R1

[0093] R1 is selected from the group consisting of hydrogen, C1-C6 alkyl, partially or fully deuterated C1-C6 alkyl or C3-C6 cycloalkyl.

[0094] R1 is preferably selected from the group consisting of hydrogen, C1-C6 alkyl and C1-C6 alkyl partially or totally deuterated.

[0095] In some modalities R1 is hydrogen.

[0096] In some embodiments R1 is C1-C6 alkyl.

[0097] In some embodiments R1 is partially deuterated C1-C6 alkyl.

[0098] In some embodiments R1 is fully deuterated C1-C6 alkyl.

[0099] In some modalities R1 is C3-C6 cycloalkyl.

[00100] R1 is preferably selected from the group consisting of hydrogen, methyl, d3-methyl, propyl and cyclopropyl.

[00101] R1 is more preferably selected from the group consisting of hydrogen, methyl and d3-methyl.

[00102] In some embodiments R1 is preferably hydrogen.

[00103] In some embodiments R1 is preferably methyl.

[00104] In some embodiments R1 is preferably d3-methyl.

[00105] R1 is most preferably hydrogen or methyl.

[00106] B2. Substitute R4 (when not combined with R5)

[00107] R4 is selected from the group consisting of hydrogen and C1-C3 alkyl.

[00108] In some modalities R4 is hydrogen.

[00109] In some embodiments R4 is C1-C3 alkyl.

[00110] R4 is preferably selected from the group consisting of hydrogen and methyl.

[00111] In some embodiments R4 is preferably hydrogen.

[00112] In some embodiments R4 is preferably methyl.

[00113] R4 is most preferably hydrogen.

[00114] B3. Substitute R5 (when not combined with R4)

[00115] R5 is hydrogen.

[00116] B4. R6 Substituent

[00117] R6 is selected from the group consisting of -COOH, -CHO, or - (CH2) m-X,

[00118] where:

[00119] m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced by;

[00120] X is hydroxy, C1-C3 alkoxy, cyano, - N = CH (NHCN) (NH2), -NH-C (pyrrolidin-1-yl) = NCN, 5 or 6 membered heteroaryl optionally substituted with a group methyl, phenyl, -SO2- R7, -NR8R9,

[00121] -CO2R10, -CH (CO2R10) 2, -CONR11R12 or -NR13COR14; on what:

[00122] R7 is C1-C3 alkyl;

[00123] R8 is hydrogen or C1-C3 alkyl;

[00124] R9 is hydrogen,

[00125] C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl, phenyl, 5 or 6 membered heterocyclyl and 5 or 6 membered heteroaryl optionally substituted with a methyl substituent,

[00126] C3-C6 cycloalkyl,

[00127] heteroaryl with 5 or 6 members, or

[00128] heterocyclyl with 5 or 6 members optionally substituted with one or two oxo substituents;

[00129] or R8 and R9 combine together with the N atom to which they are attached to form a

[00130] 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, starch, (N, N-dimethyl) acetamide and pyridyl or with one or two selected substituents fluoro and oxo, or a

[00131] heterospirocyclyl group with 9 or 10 members;

[00132] R10 is hydrogen or C1-C3 alkyl;

[00133] R11 is hydrogen or C1-C3 alkyl;

[00134] R12 is hydrogen,

[00135] C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of cyano, hydroxy, methylsulfonyl, C1-C2 alkoxy, dimethylamino, C3-C6 cycloalkyl, phenyl, 5 or 6 membered heteroaryl optionally substituted with a 5 or 6-membered methyl and heterocyclyl substituent optionally substituted with a t-Boc group or with one or two fluoro substituents,

[00136] C3-C6 cycloalkyl optionally substituted with a substituent selected from the group consisting of cyan, hydroxy, hydroxymethyl and oxo,

[00137] cyan,

[00138] methylsulfonyl,

[00139] CH2COO (C1-C3 alkyl),

[00140] heteroaryl with 5 or 6 members optionally substituted with a methyl substituent,

[00141] heterocyclyl with 4, 5 or 6 members optionally substituted with one or two substituents selected from oxo and methyl,

[00142] CH2CH (NH2) (COOH), or

[00143] CH (CH3) CONH2;

[00144] or R11 and R12 combine together with the N atom to which they are attached to form a

[00145] 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from monofluoromethyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, cyano, starch, (N, N-dimethyl) acetamide and pyridyl, or with one or two substituents selected from fluoro, methyl and oxo, or optionally fused with a cyclopropyl ring which can be substituted with one or two methyl substituents, or one

[00146] heterospirocyclyl group with 9 or 10 members;

[00147] R13 is hydrogen or C1-C3 alkyl;

[00148] R14 is C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl and phenyl,

[00149] C3-C6 cycloalkyl,

[00150] heteroaryl with 5 or 6 members, or

[00151] 5 or 6 membered heterocyclyl optionally substituted with one or two oxo substituents.

[00152] In a modality R6 is as defined above with the proviso that R9 cannot be 5 or 6 membered heterocyclyl.

[00153] In another embodiment R6 is -COOH, -CHO, or - (CH2) m-X,

[00154] where:

[00155] m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with;

[00156] X is hydroxy, C1-C3 alkoxy, cyano, - N = CH (NHCN) (NH2), -NH-C (pyrrolidin-1-yl) = NCN, 5 or 6 membered heteroaryl optionally substituted with a group methyl, phenyl, -SO2- R7, -NR8R9,

[00157] -CO2R10, -CH (CO2R10) 2, -CONR11R12 or -NR13COR14; on what:

[00158] R7 is C1-C3 alkyl;

[00159] R8 is hydrogen or C1-C3 alkyl;

[00160] R9 is hydrogen,

[00161] C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl and phenyl,

[00162] C3-C6 cycloalkyl,

[00163] heteroaryl with 5 or 6 members, or

[00164] heterocyclyl with 5 or 6 members optionally substituted with one or two oxo substituents;

[00165] or R8 and R9 combine together with the N atom to which they are attached to form a

[00166] 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, starch, (N, N-dimethyl) acetamide and pyridyl or with one or two selected substituents fluoro and oxo, or a

[00167] heterospirocyclyl group with 9 or 10 members;

[00168] R10 is hydrogen or C1-C3 alkyl;

[00169] R11 is hydrogen or C1-C3 alkyl;

[00170] R12 is hydrogen,

[00171] C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of cyano, hydroxy, methylsulfonyl, C1-C2 alkoxy, dimethylamino, C3-C6 cycloalkyl, phenyl, 5 or 6 membered heteroaryl and 5- or 6-membered heterocyclyl optionally substituted with a t-Boc group or with one or two fluoro substituents,

[00172] C3-C6 cycloalkyl optionally substituted with a substituent selected from the group consisting of cyan, hydroxy, hydroxymethyl and oxo,

[00173] cyan,

[00174] methylsulfonyl,

[00175] CH2COO (C1-C3 alkyl),

[00176] heteroaryl with 5 or 6 members,

[00177] 5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents,

[00178] CH2CH (NH2) (COOH), or

[00179] CH (CH3) CONH2;

[00180] or R11 and R12 combine together with the N atom to which they are attached to form a

[00181] 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, starch, (N, N-dimethyl) acetamide and pyridyl, or with one or two substituents selected from fluoro and oxo, or a

[00182] heterospirocyclyl group with 9 or 10 members;

[00183] R13 is hydrogen or C1-C3 alkyl;

[00184] R14 is C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl and phenyl,

[00185] C3-C6 cycloalkyl,

[00186] heteroaryl with 5 or 6 members, or

[00187] heterocyclyl with 5 or 6 members optionally substituted with one or two oxo substituents.

[00188] In some embodiments R6 is -COOH.

[00189] In some modalities R6 is -CHO.

[00190] In some embodiments R6 is - (CH2) m-X where m and X are as defined above.

[00191] R6 is preferably - (CH2) m-X where m and X are as defined above.

[00192] In some preferred embodiments R6 is -CH2-X where X is as defined above.

[00193] In some preferred embodiments R6 is as defined above -CH2CH2-X where X is as defined above.

[00194] In some preferred embodiments R6 is -CH2CH2CH2-X where X is as defined above.

[00195] In some preferred embodiments R6 is - (CH2) m-X where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- is replaced with and X is as defined above.

[00196] In some preferred embodiments R6 is - (CH2) m-X where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with and X is hydroxy.

[00197] In some preferred embodiments R6 is - (CH2) m-X where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be substituted with and X is C1-C3 alkoxy.

[00198] In some preferred embodiments R6 is - (CH2) m-X where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with and X is cyan.

[00199] In some preferred embodiments R6 is - (CH2) mX where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with and X is -N = CH ( NHCN) (NH2) or -NH-C (pyrrolidin-1-yl) = NCN.

[00200] In some preferred embodiments R6 is - (CH2) mX where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with and X is heteroaryl with 5 or 6 members optionally substituted with a methyl group.

[00201] In some preferred embodiments R6 is - (CH2) m-X where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with and X is phenyl.

[00202] In some preferred embodiments R6 is - (CH2) mX where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with and X is -SO2-R7 in that R7 is as defined above.

[00203] In some preferred embodiments R6 is - (CH2) mX where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with and X is -NR8R9 where R8 and R9 are as defined above.

[00204] In some preferred embodiments R6 is - (CH2) mX where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with and X is -CO2R10 where R10 it is as defined above.

[00205] In some preferred embodiments R6 is - (CH2) mX where m is 1, 2 or 3 and the -CH2- unit within - (CH2) m- can optionally be replaced with and X is -CH (CO2R10) 2 where R10 is as defined above.

[00206] In some preferred embodiments R6 is - (CH2) mX where m is 1, 2 or 3 and the -CH2- unit within - (CH2) m- can optionally be replaced with and X is -CONR11R12 where R11 and R12 are as defined above.

[00207] In some preferred embodiments R6 is - (CH2) mX where m is 1, 2 or 3 and the -CH2- unit within - (CH2) m- can optionally be replaced with and X is -NR13COR14 where R13 and R14 are as defined above.

[00208] R6 is preferably - (CH2) mX where m is 1, 2 or 3 and the -CH2- unit within - (CH2) m- can optionally be substituted with and X is hydroxy, ethoxy, cyano, -N = C (NHCN) (NH2), - NH-C (pyrrolidin-1-yl) = NCN, 1-methylimidazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl , tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl,

[00209] -SO2-R7, -NR8R9, -COOR10, -CH (COOR10) 2, -CONR11R12 or -NR13COR14;

[00210] where:

[00211] R7 is methyl;

[00212] R8 is hydrogen or methyl;

[00213] R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3 - yl, (tetrahydrofuran-2-yl) methyl, (1,1-dioxide) tetrahydrothiopyran-4-yl, (tetrahydro-2H-pyran-4-yl) methyl, pyridin-2-yl, pyridin-3-yl, tetrahydropyran-3-yl, cyclohexyl, (pyridin-2-yl) methyl or (1-methylpyrazol-4-

il) methyl;

[00214] or R8 and R9 combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group;

[00215] R10 is hydrogen, methyl or ethyl;

[00216] R11 is hydrogen or methyl;

[00217] R12 is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl) methyl, (pyridin-3-yl) methyl, (Nt-Boc-pyrrolidin-2-yl) methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, 2- (pyridin-2-yl) ethyl, 2- (1H-pyrazol-1-yl) ethyl, 2- (4 , 4-difluoropiperidin-1-yl) ethyl, propyl, isopropyl, 3- (N, N-dimethylamino) propyl, 3- (morpholin-1-yl) propyl, butyl, cyclopropyl, 1-cyanocyclopropyl, cyclobutyl, cyclopentyl, 2 -hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH2COOEt, tetrahydrofuran-3-yl, 2-oxotetra-hydrofuran-3-yl , tetrahydropyran-3-yl, tetrahydropyran-4-yl, (1,1-dioxide) tetrahydrothiopyran-4-yl, 1,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH2CH (NH2) (COOH), CH (CH3) CONH2, oxazol-2-yl, (pyrazine-2-yl) methyl, oxetan-3-yl, (tetrahydrofuran-2-yl) methyl, (1-methylpyrazol-4-yl) methyl, thiazol-2-yl a, 2-oxopyrrolidin-3-yl, 2-cyanocyclopentyl, isoxazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, (tetrahydropyran-4-yl) methyl, 2-oxopiperidin -3-yl, 1-methylpyrazol-4-yl, isothiazol-4-yl, 1-methyl-2-oxopiperidin-5-yl, 1-methyl-2-oxopyrrolidin-3-yl, 1-methyl-5-oxopyrrolidin -3-yl or 1-methyl-2-oxopyrrolidin-4-yl;

[00218] or R11 and R12 combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3- (fluoromethyl) group ) pyrrolidinyl, 3-methylsulfonyl-pyrrolidinyl, N, N-dimethylpyrrolidinyl-3-carboxamide, isoxazolidin-2-yl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl,

4-hydroxymethyl-piperidinyl, 4-starch-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N, N-dimethylpiperidinyl-4-carboxamide, N4-methyl-piperazinyl, N4- (N, N-dimethyl ) acetamide-piperazinyl, N4- (pyridine-2-yl) piperazinyl, morpholinyl, thiomorpholinyl, 1-oxothiomorpholinyl, 1,1-detoxothiomorpholinyl, 2-oxa-7-azospiro [4.4] nonanyl, 2-oxa-8-azaospiro [ 4.5] decanyl, 1,4-dioxa-8-azospiro [4.5] decanyl, 6,6-dimethyl-3-azabicyclo [3.1.0] hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3-oxopiperazinyl, 2- cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3-fluoromethylpyrrolidinyl or 3- (N, N-dimethylacetamide) pyrrolidinyl;

[00219] R13 is hydrogen or methyl; and

[00220] R14 is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl.

[00221] R6 is preferably - (CH2) mX where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be substituted with and X is hydroxy, ethoxy , cyano, -N = C (NHCN) (NH2), 1-methylimidazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl,

[00222] -SO2-R7, -NR8R9, -COOR10, -CH (COOR10) 2, -CONR11R12 or -NR13COR14;

[00223] where:

[00224] R7 is methyl;

[00225] R8 is hydrogen or methyl;

[00226] R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3 - yl, (1,1-dioxide) tetrahydrothiopyran-4-yl, pyridin-2-yl, pyridin-3-yl, tetrahydropyran-3-yl, cyclohexyl, (pyridin-2-yl) methyl or (1-methylpyrazol-4-yl) methyl;

[00227] or R8 and R9 combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group;

[00228] R10 is hydrogen, methyl or ethyl;

[00229] R11 is hydrogen or methyl;

[00230] R12 is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl) methyl, (pyridin-3-yl) methyl, (Nt-Boc-pyrrolidin-2-yl) methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, 2- (pyridin-2-yl) ethyl, 2- (1H-pyrazol-1-yl) ethyl, 2- (4 , 4-difluoropiperidin-1-yl) ethyl, propyl, isopropyl, 3- (N, N-dimethylamino) propyl, 3- (morpholin-1-yl) propyl, butyl, cyclopropyl, 1-cyanocyclopropyl, cyclobutyl, cyclopentyl, 2 -hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH2COOEt, tetrahydrofuran-3-yl, 2-oxotetra-hydrofuran-3-yl , tetrahydropyran-3-yl, tetrahydropyran-4-yl, (1,1-dioxide) tetrahydrothiopyran-4-yl, 1,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH2CH (NH2) (COOH), CH (CH3) CONH2, oxazol-2-yl, (pyrazine-2-yl) methyl, oxetan-3-yl, (tetrahydrofuran-2-yl) methyl, (1-methylpyrazol-4-yl) methyl, thiazol-2-yl a, 2-oxopyrrolidin-3-yl, 2-cyanocyclopentyl, isoxazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, (tetrahydropyran-4-yl) methyl, 2-oxopiperidin -3-yl, 1-methylpyrazol-4-yl, isothiazol-4-yl, 1-methyl-2-oxopiperidin-5-yl, 1-methyl-2-oxopyrrolidin-3-yl or 1-methyl-2-oxopyrrolidin -4-line;

[00231] or R11 and R12 combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3-methylsulfonyl- pyrrolidinyl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl, 4-hydroxymethyl-piperidinyl, 4-starch-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N4 methyl-piperazinyl, N4- (N, N-dimethyl) acetamide-piperazinyl, N4- (pyridine-2-yl) piperazinyl, morpholinyl, thiomorpholinyl, 1-oxidothiomorpholinyl,

1,1-dioxidothiomorpholinyl, 2-oxa-7-azospiro [4.4] nonanil, 2-oxa-8-azospiro [4.5] decanyl, 1,4-dioxa-8-azospiro [4.5] decanyl, 6,6-dimethyl- 3-azabicyclo [3.1.0] hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3-oxopiperazinyl, 2-cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3-fluoromethylpyrrolidinyl or 3- (N, N-dimethylacetamide) pyrrolidinyl;

[00232] R13 is hydrogen or methyl; and

[00233] R14 is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl.

[00234] R6 is preferably - (CH2) mX where m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be substituted with and X is hydroxy, ethoxy , cyano, -N = C (NHCN) (NH2), 1-methylimidazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl,

[00235] -SO2-R7, -NR8R9, -COOR10, -CH (COOR10) 2, -CONR11R12 or -NR13COR14; on what:

[00236] R7 is methyl;

[00237] R8 is hydrogen or methyl;

[00238] R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3 - yl, (1,1-dioxide) tetrahydrothiopyran-4-yl, pyridin-2-yl or pyridin-3-yl;

[00239] or R8 and R9 combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group;

[00240] R10 is hydrogen, methyl or ethyl;

[00241] R11 is hydrogen or methyl;

[00242] R12 is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl) methyl, (pyridin-3-yl) methyl, (Nt-Boc-pyrrolidin-2-yl) methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-

methylsulfonylethyl, 1-cyclohexylethyl, 2- (pyridin-2-yl) ethyl, 2- (1H-pyrazol-1-yl) ethyl, 2- (4,4-difluoropiperidin-1-yl) ethyl, propyl, isopropyl , 3- (N, N-dimethylamino) propyl, 3- (morpholin-1-yl) propyl, butyl, cyclopropyl, 1- cyanocyclopropyl, cyclobutyl, cyclopentyl, 2-hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl , 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH2COOEt, tetrahydrofuran-3-yl, 2-oxotetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4 -yl, (1,1-dioxide) tetrahydrothiopyran-4-yl, 1,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH2CH (NH2) (COOH) or CH (CH3) CONH2;

[00243] or R11 and R12 combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3-methylsulfonyl- pyrrolidinyl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl, 4-hydroxymethyl-piperidinyl, 4-starch-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N4 methyl-piperazinyl, N4- (N, N-dimethyl) acetamide-piperazinyl, N4- (pyridine-2-yl) piperazinyl, morpholinyl, thiomorpholinyl, 1-oxothiomorpholinyl, 1,1-detoxothiomorpholinyl, 2-oxa-7-azaospiro [ 4.4] nonanyl, 2-oxa-8-azospiro [4.5] decanyl or 1,4-dioxa-8-azospiro [4.5] decanyl;

[00244] R13 is hydrogen or methyl; and

[00245] R14 is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl.

[00246] R6 is preferably - (CH2) m-X where m is 1 or 2 and X is -NR8R9, or -CONR11R12;

[00247] where:

[00248] R8 is hydrogen or methyl;

[00249] R9 is 5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;

[00250] or R8 and R9 combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl , methylsulfonyl, starch, (N, N-dimethyl) acetamide and pyridyl or with one or two substituents selected from fluoro and oxo;

[00251] R11 is hydrogen or methyl;

[00252] R12 is heterocyclyl with 4, 5 or 6 members optionally substituted with one or two substituents selected from oxo and methyl;

[00253] or R11 and R12 combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from monofluoromethyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl , methylsulfonyl, cyano, starch, (N, N-dimethyl) acetamide and pyridyl, or with one or two substituents selected from fluoro, methyl and oxo.

[00254] R6 is most preferably - (CH2) m-X where m is 2 or 3 and X is -NR8R9;

[00255] where:

[00256] R8 is hydrogen; and

[00257] R9 is heterocyclyl with 5 or 6 members;

[00258] or R8 and R9 combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group.

[00259] B5. Substituent A

[00260] A is selected from the group consisting of C5-C7 cycloalkyl, furanyl, thiophenyl, methylthiophenyl and X1 X1 'X2 X2' X3, where:

[00261] X1 is hydrogen, halo or methyl;

[00262] X1 'is hydrogen or halo;

[00263] X2 is hydrogen, halo or methyl;

[00264] X2 'is hydrogen or halo; and

[00265] X3 is hydrogen or fluoro.

[00266] Preferably, A is X1 X1 'X2 X2' X3, where X1, X1 ', X2, X2' and X3 are as defined above.

[00267] More preferably A is

[00268] X1 X1 'X2 X2' X3, where:

[00269] X1 is hydrogen, fluoro or chloro;

[00270] X1 'is hydrogen, fluoro or chloro;

[00271] X2 is hydrogen, fluoro, chloro or bromo;

[00272] X2 'is hydrogen, fluoro, chloro or bromo; and

[00273] X3 is hydrogen or fluoro.

[00274] In a preferred embodiment not all X1, X1 ', X2, X2'

and X3 are hydrogen.

[00275] Preferably A is selected from the group consisting of.

[00276] More preferably A is selected from the group consisting of

.

[00277] Even more preferably A is selected from the group consisting of.

[00278] Most preferably A is selected from the group consisting of.

[00279] B6. Specific modalities of Formula compounds

I

[00280] Various modalities of the substituents R1, R4, R5, R6, A, X, X1, X1 ', X2, X2' and X3 have been discussed in B1 to B5 above. These "substituent" modalities can be combined with any of the "nuclear structure" modalities, discussed in B0 above, to form additional modalities of the compounds of formula Ia. All modalities of the compounds of formula Ia formed by combining the "substituent" modalities. and "nuclear structure" modalities, discussed above, are within the scope of Applicant's invention, and some additional preferred embodiments of the compounds of formula Ia are provided below.

[00281] In some modalities of formula Ia structures of formula If, Ii, and Ij are highly preferred, in which:

[00282] R1 is selected from the group consisting of hydrogen, alkyl

C1-C6 and C1-C6 alkyl partially or totally deuterated;

[00283] R4 (if present) is selected from the group consisting of hydrogen and methyl;

[00284] R5 (if present) is hydrogen;

[00285] R6 is selected from the group consisting of -COOH, -CHO,

[00286] or - (CH2) mX where m is 1, 2 or 3 and a unit of -CH2- within - (CH2) m- can optionally be replaced with eXis hydroxy, ethoxy, cyan, -N = C ( NHCN) (NH2), -NH-C (pyrrolidin-1-yl) = NCN, 1-methylimidazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl,

[00287] -SO2-R7, -NR8R9, -COOR10, -CH (COOR10) 2, -CONR11R12 or -NR13COR14; on what:

[00288] R7 is methyl;

[00289] R8 is hydrogen or methyl;

[00290] R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3 - yl, (tetrahydrofuran-2-yl) methyl, (1,1-dioxide) tetrahydrothiopyran-4-yl, (tetrahydro-2H-pyran-4-yl) methyl, pyridin-2-yl, pyridin-3-yl, tetrahydropyran-3-yl, cyclohexyl, (pyridine-2-yl) methyl or (1-methylpyrazol-4-yl) methyl;

[00291] or R8 and R9 combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group;

[00292] R10 is hydrogen, methyl or ethyl;

[00293] R11 is hydrogen or methyl;

[00294] R12 is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl) methyl, (pyridin-3-yl) methyl, (Nt-Boc-pyrrolidin-2-yl) methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-

methylsulfonylethyl, 1-cyclohexylethyl, 2- (pyridin-2-yl) ethyl, 2- (1H-pyrazol-1-yl) ethyl, 2- (4,4-difluoropiperidin-1-yl) ethyl, propyl, isopropyl , 3- (N, N-dimethylamino) propyl, 3- (morpholin-1-yl) propyl, butyl, cyclopropyl, 1- cyanocyclopropyl, cyclobutyl, cyclopentyl, 2-hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl , 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH2COOEt, tetrahydrofuran-3-yl, 2-oxotetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4 -yl, (1,1-dioxide) tetrahydrothiopyran-4-yl, 1,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH2CH (NH2) (COOH), CH (CH3) CONH2, oxazol-2-yl, (pyrazine-2-yl) methyl, oxetan-3-yl, (tetrahydrofuran-2-yl) methyl, (1-methylpyrazol-4-yl) methyl, thiazole -2-yl, 2-oxopyrrolidin-3-yl, 2-cyanocyclopentyl, isoxazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, (tetrahydropyran-4-yl) methyl, 2-oxopiperidin-3-yl, 1-methylpyrazol-4-yl, isothiazol-4-yl, 1-methyl-2-oxopiperid in-5-yl, 1-methyl-2-oxopyrrolidin-3-yl, 1-methyl-5-oxopyrrolidin-3-yl or 1-methyl-2-oxopyrrolidin-4-yl;

[00295] or R11 and R12 combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3- (fluoromethyl) group ) pyrrolidinyl, 3-methylsulfonyl-pyrrolidinyl, N, N-dimethylpyrrolidinyl-3-carboxamide, isoxazolidin-2-yl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl, 4-hydroxymethyl , 4-starch-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N, N-dimethylpiperidinyl-4-carboxamide, N4-methyl-piperazinyl, N4- (N, N-dimethyl) acetamide-piperazinyl, N4- (pyridine-2-yl) piperazinyl, morpholinyl, thiomorpholinyl, 1-oxothiomorpholinyl, 1,1-dioxidothiomorpholinyl, 2-oxa-7-azospiro [4.4] nonanyl, 2-oxa-8-azospiro [4.5] decanyl, 1 , 4-dioxa-8-azospiro [4.5] decanyl, 6,6-dimethyl-3-azabicyclo [3.1.0] hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3-oxopiperazinyl, 2-cyanopyrrolidinyl, 3-cyanopyrrolidinyl , 3 -fluoromethylpyrrolidinyl or 3- (N, N-

dimethylacetamide) pyrrolidinyl;

[00296] R13 is hydrogen or methyl; and

[00297] R14 is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl; and

[00298] Aé X1 X1 'X2 X2' X3, where:

[00299] X1 is hydrogen, halo or methyl;

[00300] X1 'is hydrogen or halo;

[00301] X2 is hydrogen, halo or methyl;

[00302] X2 'is hydrogen or halo; and

[00303] X3 is hydrogen or fluoro.

[00304] In some modalities of formula Ia structures of formula If, Ii, and Ij are highly preferred, in which:

[00305] R1 is selected from the group consisting of hydrogen, C1-C6 alkyl and C1-C6 alkyl partially or totally deuterated;

[00306] R4 (if present) is selected from the group consisting of hydrogen and methyl;

[00307] R5 (if present) is hydrogen;

[00308] R6 is selected from the group consisting of -COOH, -CHO,

[00309] or - (CH2) mX where m is 1, 2 or 3 and a unit of -CH2- within - (CH2) m- can optionally be replaced with eXis hydroxy, ethoxy, cyano, -N = C ( NHCN) (NH2), -NH-C (pyrrolidin-1-yl) = NCN, 1-methylimidazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl,

[00310] -SO2-R7, -NR8R9, -COOR10, -CH (COOR10) 2, -CONR11R12 or -NR13COR14; on what:

[00311] R7 is methyl;

[00312] R8 is hydrogen or methyl;

[00313] R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3 - yl, (1,1-dioxide) tetrahydrothiopyran-4-yl, pyridin-2-yl, pyridin-3-yl, tetrahydropyran-3-yl, cyclohexyl, (pyridine-2-yl) methyl or (1-methylpyrazol-4-yl) methyl;

[00314] or R8 and R9 combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group;

[00315] R10 is hydrogen, methyl or ethyl;

[00316] R11 is hydrogen or methyl;

[00317] R12 is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl) methyl, (pyridin-3-yl) methyl, (Nt-Boc-pyrrolidin-2-yl) methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, 2- (pyridin-2-yl) ethyl, 2- (1H-pyrazol-1-yl) ethyl, 2- (4 , 4-difluoropiperidin-1-yl) ethyl, propyl, isopropyl, 3- (N, N-dimethylamino) propyl, 3- (morpholin-1-yl) propyl, butyl, cyclopropyl, 1-cyanocyclopropyl, cyclobutyl, cyclopentyl, 2 -hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH2COOEt, tetra-

hydrofuran-3-yl, 2-oxotetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, (1,1-dioxide) tetrahydrothiopyran-4-yl, 1,3 , 4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH2CH (NH2) (COOH), CH (CH3) CONH2, oxazol-2-yl, (pyrazine-2-yl) methyl, oxetan-3-yl, (tetrahydrofuran-2-yl) methyl, (1-methylpyrazol-4-yl) methyl, thiazol-2-yl, 2-oxopyrrolidin-3-yl, 2-cyanocyclopentyl, isoxazol-4- ila, 3-methyl-1,2,4-oxadiazol-5-yl, (tetrahydropyran-4-yl) methyl, 2-oxopiperidin-3-yl, 1-methylpyrazol-4-yl, isothiazole-4-yl , 1-methyl-2-oxopiperidin-5-yl, 1-methyl-2-oxopyrrolidin-3-yl or 1-methyl-2-oxopyrrolidin-4-yl;

[00318] or R11 and R12 combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3-methylsulfonyl- pyrrolidinyl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl, 4-hydroxymethyl-piperidinyl, 4-starch-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N4 methyl-piperazinyl, N4- (N, N-dimethyl) acetamide-piperazinyl, N4- (pyridine-2-yl) piperazinyl, morpholinyl, thiomorpholinyl, 1-oxothiomorpholinyl, 1,1-detoxothiomorpholinyl, 2-oxa-7-azaospiro [ 4.4] nonanyl, 2-oxa-8-azospiro [4.5] decanyl, 1,4-dioxa-8-azospiro [4.5] decanyl, 6,6-dimethyl-3-azabicyclo [3.1.0] hexanyl, piperazinyl, 3- oxopiperazinyl, 4-methyl-3-oxopiperazinyl, 2-cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3-fluoromethylpyrrolidinyl or 3- (N, N-dimethylacetamide) pyrrolidinyl;

[00319] R13 is hydrogen or methyl; and

[00320] R14 is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl; and

[00321] Aerial

X1 X1 'X2 X2' X3, where:

[00322] X1 is hydrogen, halo or methyl;

[00323] X1 'is hydrogen or halo;

[00324] X2 is hydrogen, halo or methyl;

[00325] X2 'is hydrogen or halo; and

[00326] X3 is hydrogen or fluoro.

[00327] In some modalities of formula Ia structures of formula If, Ii, and Ij are highly preferred, in which:

[00328] R1 is selected from the group consisting of hydrogen, C1-C6 alkyl and C1-C6 alkyl partially or totally deuterated.

[00329] R4 (if present) is selected from the group consisting of hydrogen and methyl.

[00330] R5 (if present) is hydrogen.

[00331] R6 is selected from the group consisting of -COOH, -CHO,

[00332] or - (CH2) mX where m is 1, 2 or 3 and a unit of -CH2- within - (CH2) m- can optionally be replaced with eXis hydroxy, ethoxy, cyan, -N = C ( NHCN) (NH2), -NH-C (pyrrolidin-1-yl) = NCN, 1-methylimidazol-2-yl, 3-methyl-1,2,4-

oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl,

[00333] -SO2-R7, -NR8R9, -COOR10, -CH (COOR10) 2, -CONR11R12 or -NR13COR14; on what:

[00334] R7 is methyl;

[00335] R8 is hydrogen or methyl;

[00336] R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3 - yl, (1,1-dioxide) tetrahydrothiopyran-4-yl, pyridin-2-yl or pyridin-3-yl;

[00337] or R8 and R9 combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group;

[00338] R10 is hydrogen, methyl or ethyl;

[00339] R11 is hydrogen or methyl;

[00340] R12 is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl) methyl, (pyridin-3-yl) methyl, (Nt-Boc-pyrrolidin-2-yl) methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, 2- (pyridin-2-yl) ethyl, 2- (1H-pyrazol-1-yl) ethyl, 2- (4 , 4-difluoropiperidin-1-yl) ethyl, propyl, isopropyl, 3- (N, N-dimethylamino) propyl, 3- (morpholin-1-yl) propyl, butyl, cyclopropyl, 1-cyanocyclopropyl, cyclobutyl, cyclopentyl, 2 -hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH2COOEt, tetrahydrofuran-3-yl, 2-oxotetra-hydrofuran-3-yl , tetrahydropyran-3-yl, tetrahydropyran-4-yl, (1,1-dioxide) tetrahydrothiopyran-4-yl, 1,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH2CH (NH2) (COOH) or CH (CH3) CONH2;

[00341] or R11 and R12 combine together with the N atom to which they are attached to form a pyrrolidinyl group, 2-

hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3-methylsulfonyl-pyrrolidinyl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperiperinyl, 4-hydroxy starch-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N4-methyl-piperazinyl, N4- (N, N-dimethyl) acetamide-piperazinyl, N4- (pyridine-2-yl) piperazinyl, morpholinyl, thiomorpholinyl, 1-oxothiomorpholinyl, 1,1-detoxothiomorpholinyl, 2-oxa-7-azospiro [4.4] nonanil, 2-oxa-8-azospiro [4.5] decanyl or 1,4-dioxa-8-azospiro [4.5] decanyl;

[00342] R13 is hydrogen or methyl; and

[00343] R14 is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl

[00344] Aé X1 X1 'X2 X2' X3,

[00345] where:

[00346] X1 is hydrogen, halo or methyl;

[00347] X1 'is hydrogen or halo;

[00348] X2 is hydrogen, halo or methyl;

[00349] X2 'is hydrogen or halo; and

[00350] X3 is hydrogen or fluoro.

[00351] In other modalities of formula Ia structures of formula If, Ii, and Ij are highly preferred

,

[00352] where:

[00353] R1 is selected from the group consisting of hydrogen and methyl;

[00354] R4 (if present) is hydrogen;

[00355] R5 (if present) is hydrogen;

[00356] R6 is - (CH2) m-X where m is 1 or 2 and X is -NR8R9, or - CONR11R12;

[00357] where:

[00358] R8 is hydrogen or methyl;

[00359] R9 is 5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;

[00360] or R8 and R9 combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl , methylsulfonyl, starch, (N, N-dimethyl) acetamide and pyridyl or with one or two substituents selected from fluoro and oxo;

[00361] R11 is hydrogen or methyl;

[00362] R12 is heterocyclyl with 4, 5 or 6 members optionally substituted with one or two substituents selected from oxo and methyl;

[00363] or R11 and R12 combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from monofluoromethyl, trifluoromethyl, hydroxy, hydroxymethyl,

methoxymethyl, methylsulfonyl, cyano, starch, (N, N-dimethyl) acetamide and pyridyl, or with one or two substituents selected from fluoro, methyl and oxo; and

[00364] A is selected from the group consisting of.

[00365] In other modalities of formula Ia structures of formula If are highly preferred,

[00366] where:

[00367] R1 is selected from the group consisting of hydrogen and methyl;

[00368] R4 is hydrogen;

[00369] R5 is hydrogen;

[00370] R6 is - (CH2) m-X where m is 2 or 3 and X is -NR8R9;

[00371] where:

[00372] R8 is hydrogen; and

[00373] R9 is heterocyclyl with 5 or 6 members;

[00374] or R8 and R9 combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group; and

[00375] A is selected from the group consisting of.

[00376] Especially preferred embodiments of the compounds of formula Ia are described in Examples 1 to 478 below. When these examples describe the preparation of a compound of formula Ia in the form of a pharmaceutically acceptable salt or solvate, it will be understood that the present invention also relates to said compound in the form of the corresponding free acid or free base. Similarly, when these examples describe the preparation of a compound of formula Ia in the form of a free acid or free base, it will be understood that the present invention also relates to said compound in the form of a pharmaceutically acceptable salt or solvate thereof.

[00377] The non-saline, unsolvated forms of Examples 1 to 478 are listed below. The invention also relates to the pharmaceutically acceptable salts or solvates of each of these individual compounds. If any of these compounds exist as tautomers, each tautomeric form, and mixtures thereof, are contemplated as included in the present invention.

[00378] Example 1: 2- (6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl (S) -ethyl acetate

[00379] Example 2: 2- (6- (2,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl (S) -ethyl acetate

[00380] Example 3: (S) -2- (6- (2,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [1,2-c] imidazol-1-yl) acetic

[00381] Example 4: 2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) methyl acetate

[00382] Example 5: 2 - ((5aS, 6aR) -5a- (3,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) methyl acetate

[00383] Example 6: 2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa acid [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic

[00384] Example 7: 2 - ((5aS, 6aR) -5a- (3,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa acid [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic.

[00385] Example 8: (5aS, 6aR) -5a- (3,5-difluorophenyl) -1- (2-hydroxyethyl) - 5.5a, 6.6a-tetrahydrocyclopropa [3,4] pyrrole [1, 2-c] imidazole-3 (2H) -thione

[00386] Example 9: (S) -2- (6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole -1-yl) -1-morpholinoethanone

[00387] Example 10: (S) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [1, 2-c] imidazol-1-yl) acetic

[00388] Example 11: (S) -2- (6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [1,2-c] imidazol-1-yl) acetic

[00389] Example 12: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1, 2-c] imidazol-1-yl) acetic

[00390] Example 13: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1, 2-c] imidazol-1-yl) acetic

[00391] Example 14: (R) -2- (6- (2,5-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1,2-c] imidazol-1-yl) acetic

[00392] Example 15: (R) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1, 2-c] imidazol-1-yl) acetic

[00393] Example 16: (S) -2- (6- (5-bromo-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1,2- c] imidazol-1-yl) acetic

[00394] Example 17: (R) -2- (6- (5-chloro-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1,2- c] imidazol-1-yl) acetic

[00395] Example 18: (R) -2- (6- (2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1,2-c] imidazol-1-yl) acetic

[00396] Example 19: (S) -N-cyano-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [1,2-c] imidazol-1-yl) acetamide

[00397] Example 20: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (methylsulfonyl) acetamide

[00398] Example 21: (S) -2- (6- (5-bromo-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -N- (methylsulfonyl) acetamide

[00399] Example 22: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-oxotetrahydrofuran-3-yl) acetamide

[00400] Example 23: (R) -N- (methylsulfonyl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H -pyrrole [1,2-c] imidazol-1-yl) acetamide

[00401] Example 24: (R) -2- (6- (2,5-difluorophenyl) -3-thioxo-2,5,6,7-tetra-

hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (methylsulfonyl) acetamide

[00402] Example 25: (R) - (2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] ethyl imidazol-1-yl) acetyl) glycinate

[00403] Example 26: (S) -2- (2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo- 2,5,6,7-tetrahydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) acetamido) propanamide

[00404] Example 27: (R) -N- (cyanomethyl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazol-1-yl) acetamide

[00405] Example 28: N - ((1r, 4R) -4-hydroxycyclohexyl) -2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5 , 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00406] Example 29: N- (2-hydroxycyclohexyl) -2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00407] Example 30: (R) -N, N-dimethyl-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazol-1-yl) acetamide

[00408] Example 31: (S) -2-amino-3- (2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7 -tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) acetamido) propanoic

[00409] Example 32: ((R) -N-cyclopentyl-2- (6- (2,3,5,6-tetrafluorophenyl) - 3-thioxo-3,5,6,7-tetrahydro-2H- pyrrole [1,2-c] imidazol-1-yl) acetamide

[00410] Example 33: 2 - ((5aS, 6aR) -5a- (3,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetamide

[00411] Example 34: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo 3,5,6,7-tetrahydro-2H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-oxocyclopentyl) acetamide

[00412] Example 35: (5aS, 6aR) -1- (2-aminoethyl) -5a- (3,5-difluorophenyl) -5.5a, 6.6a-tetrahydrocyclopropa [3,4] pyrrole [1, 2-c] imidazole-

3 (2H) -thione

[00413] Example 36: 2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetonitrile

[00414] Example 37: N-benzyl-2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N-methylacetamide

[00415] Example 38: N-butyl-2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N-methylacetamide

[00416] Example 39: (5aS, 6aR) -1- (2- (butyl (methyl) amino) ethyl) -5a- (2,5-difluorophenyl) -5,5a, 6,6a-tetrahydrocyclopropa [3 , 4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00417] Example 40: (5aS, 6aR) -1- (2- (benzyl (methyl) amino) ethyl) -5a- (2,5-difluorophenyl) -5,5a, 6,6a-tetrahydrocyclopropa [3 , 4] pyrrole [1,2- c] imidazole-3 (2H) -thione

[00418] Example 41: (5aS, 6aR) -1 - ((1H-tetrazol-5-yl) methyl) -5a- (2,5-difluorophenyl) -5,5a, 6,6a-tetrahydrocyclopropa [3 , 4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00419] Example 42: (5aS, 6aR) -5a- (2,5-difluorophenyl) -1- (2-hydroxyethyl) -5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1, 2-c] imidazole-3 (2H) -thione

[00420] Example 43: (S) -6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole-1 -carboxylic

[00421] Example 44: 2- (5a- (thiophen-2-yl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c ] imidazol-1-yl) ethyl acetate

[00422] Example 45: (S) -6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole-1- carbaldehyde

[00423] Example 46: (S) -1- (hydroxymethyl) -6- (2,3,5,6-tetrafluorophenyl) - 6,7-dihydro-2H-pyrrolo [1,2-c] imidazole- 3 (5H) -thione

[00424] Example 47: (S) -1- (methylsulfonylmethyl) -6- (2,3,5,6-tetrafluorophenyl) -6,7-dihydro-2H-pyrrolo [1,2-c] imidazole- 3 (5H) -thione

[00425] Example 48: (5aS, 6aR) -5a- (2,5-difluorophenyl) -1-phenethyl-5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00426] Example 49: (5aS, 6aR) -5a- (2,5-difluorophenyl) -1- (3-phenylpropyl) -5.5a, 6.6a-tetrahydrocyclopropa [3,4] pyrrole [1, 2-c] imidazole-3 (2H) -thione

[00427] Example 50: (5aS, 6aR) -5a- (3,5-difluorophenyl) -1- (hydroxymethyl) -5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1,2- c] imidazole-3 (2H) -thione

[00428] Example 51: 2 - ((5aS, 6aR) -5a- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocycloprop acid [ 3.4] pyrrole [1,2-c] imidazol-1-yl) acetic

[00429] Example 52: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocycloprop acid [3, 4] pyrrole [1,2-c] imidazol-1-yl) acetic

[00430] Example 53: 2 - ((5aS, 6aR) -5a- (3-chloro-5-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocycloprop acid [3, 4] pyrrole [1,2-c] imidazol-1-yl) acetic

[00431] Example 54: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) ethyl acetate

[00432] Example 55: 2 - ((5aS, 6aR) -5a- (3-chloro-5-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) ethyl acetate

[00433] Example 56: (2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3, 4] pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00434] Example 57: 2 - ((5aS, 6aR) -5a- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazole-1-

il) acetamide

[00435] Example 58: 2 - ((5aS, 6aR) -5a- (3-chloro-5-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) acetamide

[00436] Example 59: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) ethyl acetate

[00437] Example 60: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) ethyl acetate

[00438] Example 61: (R) -2- (6- (2,5-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole -1-yl) ethyl acetate

[00439] Example 62: (S) -2- (6- (5-bromo-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) ethyl acetate

[00440] Example 63: (R) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) ethyl acetate

[00441] Example 64: (R) -2- (6- (5-chloro-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) ethyl acetate

[00442] Example 65: (R) -2- (6- (2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole -1-yl) ethyl acetate

[00443] Example 66: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) -1- morpholinoetan-1-one

[00444] Example 67: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) -N- isopropylacetamide

[00445] Example 68: 2 - ((5aS, 6aR) -5a- (3-chloro-5-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) -N-methylacetamide

[00446] Example 69: 2 - ((5aS, 6aR) -5a- (3-chloro-5-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) -N, N-dimethylacetamide

[00447] Example 70: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - 1- (pyrrolidin-1-yl) ethan-1-one

[00448] Example 71: (R) -N- (3- (dimethylamino) propyl) -2- (6- (2,3,5,6- tetrafluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00449] Example 72: (R) -N- (2-hydroxyethyl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00450] Example 73: (R) -N- (2-methoxyethyl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00451] Example 74: (S) -2- (6- (5-bromo-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -N-cyclopentylacetamide

[00452] Example 75: 2 - ((R) -6- (5-chloro-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00453] Example 76: (R) -N-cyclopentyl-2- (6- (2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) acetamide

[00454] Example 77: 2 - ((R) -6- (2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole -1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00455] Example 78 (: ((R) -N-cyclopropyl-2- (6- (2,3,5,6-tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H- pyrrole [1,2-c] imidazol-1-yl) acetamide

[00456] Example 79: (R) -N- (cyclopropylmethyl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazol-1-yl) acetamide

[00457] Example 80: (R) -N-cyclobutyl-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) acetamide

[00458] Example 81: (R) -1- (4-methylpiperazin-1-yl) -2- (6- (2,3,5,6-

tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[00459] Example 82: (R) -1- (4-hydroxypiperidin-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[00460] Example 83: (R) -1- (4- (hydroxymethyl) piperidin-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[00461] Example 84: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-cyclopentylacetamide

[00462] Example 85: (R) -N, N-dimethyl-2- (4- (2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) piperazin-1-yl) acetamide

[00463] Example 86: (R) -1- (2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [ 1,2-c] imidazol-1-yl) acetyl) piperidine-4-carboxamide

[00464] Example 87: (R) -1- (1,4-dioxa-8-azospiro [4.5] decan-8-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2- c] imidazol-1-yl) ethan-1-one

[00465] Example 88: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-isopropylacetamide

[00466] Example 89: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (3-morpholinopropyl) acetamide

[00467] Example 90: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00468] Example 91: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (4-methylpiperazin-1-yl) ethan-1-one

[00469] Example 92: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-butyl-N-methylacetamide

[00470] Example 93: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-hydroxyethyl) acetamide

[00471] Example 94: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-cyclopropylacetamide

[00472] Example 95: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (cyclopropylmethyl) acetamide

[00473] Example 96: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) acetamide

[00474] Example 97: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-propylacetamide

[00475] Example 98: 1 - ((S) -2- (hydroxymethyl) pyrrolidin-1-yl) -2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo- 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[00476] Example 99: (S) -N-cyclobutyl-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) acetamide

[00477] Example 100: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1 - ((S) -2- (hydroxymethyl) pyrrolidin-1-yl) ethan-1-one

[00478] Example 101: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (pyrrolidin-1-yl) ethan- 1-one

[00479] Example 102: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-cyclobutylacetamide

[00480] Example 103: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-

methoxyethyl) acetamide

[00481] Example 104: (R) -1- (pyrrolidin-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[00482] Example 105: (S) -1- (pyrrolidin-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[00483] Example 106: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2- (pyridin-2-yl) ethyl) acetamide

[00484] Example 107: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-methoxyethyl) acetamide

[00485] Example 108: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) acetamide

[00486] Example 109: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (pyridin-3-ylmethyl) acetamide

[00487] Example 110: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (pyrrolidin-1-yl) ethan- 1-one

[00488] Example 111: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (4,4-difluoropiperidin-1-yl) ethan-1-one

[00489] Example 112: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (1,1-dioxidotetrahydro-2H-thiopyran-4-yl) acetamide

[00490] Example 113: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2,2,2-trifluoroethyl) acetamide

[00491] Example 114: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2- (methylsulfonyl) ethyl) acetamide

[00492] Example 115: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2- (4,4-difluoropiperidin-1-yl) ethyl) acetamide

[00493] Example 116: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00494] Example 117: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (4,4-difluoropiperidin-1-yl) ethan-1-one

[00495] Example 118: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2- (methylsulfonyl) ethyl) acetamide

[00496] Example 119: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-hydroxyethyl) acetamide

[00497] Example 120: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2- (hydroxymethyl) cyclopentyl) acetamide

[00498] Example 121: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (3-hydroxypiperidin-1-yl) ethan-1-one

[00499] Example 122: (R) -2 - ((2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) acetamido) methyl) tert-butyl pyrrolidine-1-carboxylate

[00500] Example 123: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (4- (methylsulfonyl) piperidin-1-yl) ethan-1-one

[00501] Example 124: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (pyridin-3-ylmethyl) acetamide

[00502] Example 125: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (1,1-dioxidothiomorpholine) ethan-1-one

[00503] Example 126: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (4- (methylsulfonyl) piperidin-1-yl) ethan-1-one

[00504] Example 127: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -1-cyclohexylethyl) acetamide

[00505] Example 128: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[00506] Example 129: (R) -N- (1,1-dioxidotetrahydro-2H-thiopyran-4-yl) - 2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00507] Example 130: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (1,1-dioxidotetrahydro-2H-thiopyran-4-yl) acetamide

[00508] Example 131: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-hydroxyethyl) -N- methylacetamide

[00509] Example 132: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-cyclohexyl-N-methylacetamide

[00510] Example 133: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-isopropylacetamide

[00511] Example 134: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-

2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N-methyl-N- (pyridin-3-ylmethyl) acetamide

[00512] Example 135: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (3- (methylsulfonyl) pyrrolidin-1-yl) ethan-1-one

[00513] Example 136: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (1,1-dioxidothiomorpholine) ethan-1-one

[00514] Example 137: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-thiomorfolinoetan-1-one

[00515] Example 138: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (2-oxa-7- azaespiro [4.4] nonan-7-yl) etan-1-one

[00516] Example 139: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (pyridin-2-ylmethyl) acetamide

[00517] Example 140: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-morpholinoetan-1-one

[00518] Example 141: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-morpholinoetan-1-one

[00519] Example 142: N- (2- (1H-pyrazol-1-yl) ethyl) -2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00520] Example 143: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - N- (cyclopropylmethyl) acetamide

[00521] Example 144: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N- (cyanomethyl) acetamide

[00522] Example 145: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N- (2- (pyridin-2-yl) ethyl) acetamide

[00523] Example 146: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - N- (3- (dimethylamino) propyl) acetamide

[00524] Example 147: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - 1- (4- (pyridin-2-yl) piperazin-1-yl) etan-1-one

[00525] Example 148: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N- (tetrahydrofuran-3-yl) acetamide

[00526] Example 149: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxy-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - 1- (4,4-difluoropiperidin-1-yl) etan-1-one

[00527] Example 150: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N- (2,2,2-trifluoroethyl) acetamide

[00528] Example 151: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N- (pyridin-3-ylmethyl) acetamide

[00529] Example 152: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N- (2,2,2-trifluoroethyl) acetamide

[00530] Example 153: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - N-cyclobutylacetamide

[00531] Example 154: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - N-cyclopropylacetamide

[00532] Example 155: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - N-cyclopentyl-N-methylacetamide

[00533] Example 156: N-benzyl-2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00534] Example 157: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - 1-morpholinoetan-1-one

[00535] Example 158: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - 1- (piperidin-1-yl) ethan-1-one

[00536] Example 159: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (cyanomethyl) acetamide

[00537] Example 160: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((1R, 2R) -2-hydroxycyclohexyl) acetamide

[00538] Example 161: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((1S, 2S) -2-hydroxycyclopentyl) acetamide

[00539] Example 162: (S) -N- (2- (1H-pyrazol-1-yl) ethyl) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2, 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00540] Example 163: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (1,1-dioxidotetrahydro-2H-thiopyran-4-yl) -N-methylacetamide

[00541] Example 164: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (3- (methylsulfonyl) pyrrolidin-1-yl) ethan-1-one

[00542] Example 165: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (2-oxa-8- azaespiro [4.5] decan-8-yl) etan-1-one

[00543] Example 166: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (1-oxothiomorpholine) ethan-1-one

[00544] Example 167: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[00545] Example 168: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (1,3,4-thiadiazol-2-yl) acetamide

[00546] Example 169: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (pyridin-2-yl) acetamide

[00547] Example 170: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N- (pyridin-2-yl) acetamide

[00548] Example 171: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N- (pyridin-3-yl) acetamide

[00549] Example 172: (R) -1- (2-hydroxyethyl) -6- (2,3,5,6-tetrafluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazole-3-thione

[00550] Example 173: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2-hydroxyethyl) -2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazole-3-thione

[00551] Example 174: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -1- (2-morpholinoethyl) -5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [ 1,2-c] imidazole-3 (2H) -thione

[00552] Example 175: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -1- (2- (isopropylamino) ethyl) -5.5a, 6.6a-tetrahydrocyclopropa [3,4 ] pyrrole [1,2-

c] imidazole-3 (2H) -thione

[00553] Example 176: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2 - ((((R) - tetrahydrofuran-3-yl) amino) ethyl) -2, 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00554] Example 177: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2- (4,4-difluoropiperidin-1-yl) ethyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00555] Example 178: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2 - ((1,1-dioxidotetrahydro-2H-thiopyran-4-yl) amino) ethyl ) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00556] Example 179: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2- (4- (methylsulfonyl) piperidin-1-yl) ethyl) -2,5,6, 7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00557] Example 180: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- ((2,2,2-trifluoroethyl) amino) ethyl) -5,5a, 6, 6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00558] Example 181: (S) -6- (3-bromo-2,6-difluorophenyl) -1- (2- (cyclobutylamino) ethyl) -2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazole-3-thione

[00559] Example 182: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2 - ((2- (methylsulfonyl) ethyl) amino) ethyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2- c] imidazole-3-thione

[00560] Example 183: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2 - ((2-hydroxyethyl) (methyl) amino) ethyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2- c] imidazole-3-thione

[00561] Example 184: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2 - ((((R) -1- cyclohexylethyl) amino) ethyl) -2,5, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00562] Example 185: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (pyrrolidin-1-yl) ethyl) -5.5a, 6.6a-tetrahydrocyclopropa [3.4] pyrrole [1,2-

c] imidazole-3 (2H) -thione

[00563] Example 186: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- ((cyclopropylmethyl) amino) ethyl) -5.5a, 6.6a-tetrahydrocyclopropa [ 3.4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00564] Example 187: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (cyclopropylamino) ethyl) -5.5a, 6.6a-tetrahydrocyclopropa [3,4 ] pyrrole [1,2- c] imidazole-3 (2H) -thione

[00565] Example 188: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (cyclobutylamino) ethyl) -5.5a, 6.6a-tetrahydrocyclopropa [3,4 ] pyrrole [1,2- c] imidazole-3 (2H) -thione

[00566] Example 189: (5aS, 6aR) -1- (2- (benzylamino) ethyl) -5a- (5-chloro-2-fluorophenyl) -5.5a, 6.6a-tetrahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00567] Example 190: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (cyclopentyl (methyl) amino) ethyl) -5.5a, 6.6a-tetrahydrocyclopropa [3.4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00568] Example 191: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2-morpholinoethyl) -5.5a, 6.6a-tetrahydrocycloprop [3,4] pyrrole [ 1,2-c] imidazole-3 (2H) -thione

[00569] Example 192: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (pyridin-2-ylamino) ethyl) -5.5a, 6.6a-tetrahydrocyclopropa [3.4] pyrrole [1,2- c] imidazole-3 (2H) -thione

[00570] Example 193: (S) -6- (3-chloro-2,6-difluorophenyl) -1- (2- (methylamino) ethyl) -2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazole-3-thione

[00571] Example 194: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -1- (2- (piperidin-1-yl) ethyl) -5.5a, 6.6a-tetrahydrocyclopropa [3.4] pyrrole [1,2- c] imidazole-3 (2H) -thione

[00572] Example 195: (S) -6- (3-bromo-2,6-difluorophenyl) -1- (2-morpholinoethyl) -2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazole-3-thione

[00573] Example 196: (S) -6- (3-chloro-2,6-difluorophenyl) -1- (2-

morpholinoethyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00574] Example 197: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -1- (2- (pyridin-3-ylamino) ethyl) -5.5a, 6.6a-tetrahydrocyclopropa [3.4] pyrrole [1,2- c] imidazole-3 (2H) -thione

[00575] Example 198: (R) -1- (2- (pyrrolidin-1-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[00576] Example 199: (R) -1- (2-morpholinoethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazole-3-thione

[00577] Example 200: 2 - ((6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [1,2-c] (R) -diethyl imidazol-1-yl) methyl) malonate

[00578] Example 201: (R) -2 - ((6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1 , 2-c] imidazol-1-yl) methyl) malonic

[00579] Example 202: (R) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1, 2-c] imidazol-1-yl) propanoic

[00580] Example 203: (R) -N- (cyclopropylmethyl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazol-1-yl) propanamide

[00581] Example 204: (R) -1- (pyrrolidin-1-yl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one

[00582] Example 205: (R) -1-morpholino-3- (6- (2,3,5,6-tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) propan-1-one

[00583] Example 206: (R) -1- (4,4-difluoropiperidin-1-yl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one

[00584] Example 207: (R) -1- (piperidin-1-yl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one

[00585] Example 208: (R) -1- (4-methylpiperidin-1-yl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazole-1-

il) propan-1-one

[00586] Example 209: (R) -1- (morpholinomethyl) -6- (2,3,5,6-tetrafluorophenyl) -6,7-dihydro-2H-pyrrolo [1,2-c] imidazole- 3 (5H) -thione

[00587] Example 210: (R) -1- (pyrrolidin-1-ylmethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole [ 1,2-c] imidazole-3-thione

[00588] Example 211: (R) -1 - ((((2-hydroxyethyl) (methyl) amino) methyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00589] Example 212: (R) -1- (2- (pyridin-3-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -6,7-dihydro-2H-pyrrole [1,2-c] imidazole-3 (5H) -thione

[00590] Example 213: (R) -1- (2- (pyridin-2-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[00591] Example 214: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2- (pyridin-3-yl) ethyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[00592] Example 215: (S) -6- (3-chloro-2,6-difluorophenyl) -1- (2- (pyridin-3-yl) ethyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[00593] Example 216: (R) -1- (3-ethoxypropyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazole-3-thione

[00594] Example 217: (R) -1- (2- (1-methyl-1H-imidazol-2-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00595] Example 218: (R) -1- (2- (pyridin-4-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[00596] Example 219: (R) -1- (3- (pyrrolidin-1-yl) propyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[00597] Example 220: (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo 3,5,6,7-tetrahydro-2H-pyrrole [1, 2-c] imidazol-1-yl) methyl) cyclopropanecarboxamide

[00598] Example 221: (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo 3,5,6,7-tetrahydro-2H-pyrrole [1, 2-c] imidazole-1-

il) methyl) cyclopropanecarboxamide

[00599] Example 222: (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazol-1-yl) methyl) tetrahydro-2H-pyran-4-carboxamide

[00600] Example 223: (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazol-1-yl) methyl) nicotinamide

[00601] Example 224: 2 - {[(6S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo- 2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazol-1-yl] methyl} -1-cyanoguanidine

[00602] Example 225: (S, Z) -N - ((6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [ 1,2-c] imidazol-1-yl) methyl) -N'- cyanopyrrolidine-1-carboxyidamide

[00603] Example 226: (S) -N- (2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [ 1,2-c] imidazol-1-yl) ethyl) -N- methylnicotinamide

[00604] Example 227: (S) -N- (2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [ 1,2-c] imidazol-1-yl) ethyl) -N-methylpyrrolidine-1-carboxamide

[00605] Example 228: (S) -6- (3-chloro-2,6-difluorophenyl) -1 - ((3-methyl-1,2,4-oxadiazol-5-yl) methyl) -6.7 -dihydro-2H-pyrrolo [1,2-c] imidazole-3 (5H) - thiona

[00606] Example 229: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H- acid pyrrole [1,2-c] imidazol-1-yl) acetic

[00607] Example 230: (S) -2- (6- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [ 1,2-c] imidazol-1-yl) acetic

[00608] Example 231: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6- hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic

[00609] Example 232: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetra-

hydrofuran-3-yl) acetamide

[00610] Example 233: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1-morpholinoetan-1-one

[00611] Example 234: 1 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) cyclopropane-1-carboxamide

[00612] Example 235: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1- (1,1-dioxidothiomorpholine) ethan-1-one

[00613] Example 236: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- isopropylacetamide

[00614] Example 237: (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -1-morpholinoetan-1-one

[00615] Example 238: (S) -1- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (2- (methylsulfonyl) ethyl) cyclopropane-1-carboxamide

[00616] Example 239: (R) -N- (1,1-dioxidotetrahydro-2H-thiopyran-4-yl) - 2- (2-methyl-3-thioxo-6- (2,3,6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00617] Example 240: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) acetamide

[00618] Example 241: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1 - ((S) -2- (hydroxymethyl) pyrrolidin-1-yl) ethan-1-one

[00619] Example 242: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1-morpholinoetan-1-one

[00620] Example 243: 2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-

thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00621] Example 244: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00622] Example 245: (R) -2- (6- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N-cyclopentylacetamide

[00623] Example 246: 2 - ((R) -6- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00624] Example 247: 1 - ((S) -2- (methoxymethyl) pyrrolidin-1-yl) -2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl ) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[00625] Example 248: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -1 - ((S) -2- (trifluoromethyl) pyrrolidin-1-yl) etan-1-one

[00626] Example 249: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) acetamide

[00627] Example 250: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00628] Example 251: 2 - ((S) -6- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00629] Example 252: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[00630] Example 253: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (cyanomethyl) acetamide

[00631] Example 254: (R) -N- (1-cyanocyclopropyl) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00632] Example 255: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[00633] Example 256: (S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-1- (2- (((R) -tetrahydrofuran-3-yl) amino) ethyl ) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00634] Example 257: (R) -2-methyl-1- (2-morpholinoethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H- pyrrole [1,2-c] imidazole-3-thione

[00635] Example 258: (S) -2-amino-3- (2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamido) propanoic

[00636] Example 259: (R) -2-methyl-1- (2- (pyridin-3-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -6,7-dihydro -2H-pyrrolo [1,2-c] imidazole-3 (5H) -thione

[00637] Example 260: (R) -3- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H- acid pyrrole [1,2-c] imidazol-1-yl) propanoic

[00638] Example 261: (R) -3- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1- (pyrrolidin-1-yl) propan-1-one

[00639] Example 262: (S) -3- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) propanamide

[00640] Example 263: (R) -3- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) propanamide

[00641] Example 264: (R) -3- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (pyrrolidin-1-yl) propan-1-one

[00642] Example 265: 3 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -

2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) propanamide

[00643] Example 266: (R) -3- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -1-morpholinopropan-1-one

[00644] Example 267: 1 - ((S) -2- (hydroxymethyl) pyrrolidin-1-yl) -3 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl ) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one

[00645] Example 268: (S) -3- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (pyridin-2-yl) propanamide

[00646] Example 269: (R) -3- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (pyridin-2-yl) propanamide

[00647] Example 270: (R) -N- (cyanomethyl) -3- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) propanamide

[00648] Example 271: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrole [1,2- c] imidazol-1-yl) -N-cyclopentylacetamide

[00649] Example 272: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N-cyclopentylacetamide

[00650] Example 273: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N-cyclopentylacetamide

[00651] Example 274: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00652] Example 275: acid 2 - ((5aS, 6aR) -5a- (5-bromo-2-

fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic

[00653] Example 276: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) - 2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa- hydrocycloprop [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic

[00654] Example 277: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[00655] Example 278: 2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[00656] Example 279: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00657] Example 280: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00658] Example 281: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00659] Example 282: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00660] Example 283: 1 - ((S) -2- (methoxymethyl) pyrrolidin-1-yl) -2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[00661] Example 284: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N-isopropylacetamide

[00662] Example 285: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-

thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (1,3,4-thiadiazol-2-yl) acetamide

[00663] Example 286: (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (oxazol-2-yl) acetamide

[00664] Example 287: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (pyridin-4-yl) acetamide

[00665] Example 288: 3 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) propanamide

[00666] Example 289: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00667] Example 290: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (pyridin-3-ylmethyl) acetamide

[00668] Example 291: (S) -N- (benzo [d] [1,3] dioxol-5-ylmethyl) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl- 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00669] Example 292: 1 - ((R) -3-fluoropyrrolidin-1-yl) -2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2 , 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[00670] Example 293: (R) -N- (2-hydroxyethyl) -N-methyl-2- (2-methyl-3-thioxo- 6- (2,3,6-trifluorophenyl) -2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00671] Example 294: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-cyclohexylacetamide

[00672] Example 295: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,5,6-

tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N - ((S) - tetrahydrofuran-3-yl) acetamide

[00673] Example 296: 1 - ((S) -2- (fluoromethyl) pyrrolidin-1-yl) -2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl ) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[00674] Example 297: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00675] Example 298: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N- (2,2,2-trifluoroethyl) acetamide

[00676] Example 299: (R) -2- (2-methyl-6- (2,3,6-trifluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00677] Example 300: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N- (2,2,2-trifluoroethyl) acetamide

[00678] Example 301: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[00679] Example 302: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-cyclohexylacetamide

[00680] Example 303: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N-isopropylacetamide

[00681] Example 304: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N- (cyanomethyl) acetamide

[00682] Example 305: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-

methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- (cyanomethyl) acetamide

[00683] Example 306: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00684] Example 307: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N - ((R) -tetrahydrofuran-3-yl) acetamide

[00685] Example 308: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00686] Example 309: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -1- (pyrrolidin-1-yl) ethan-1-one

[00687] Example 310: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -1- (pyrrolidin-1-yl) ethan-1-one

[00688] Example 311: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (piperidin-1-yl) ethan-1-one

[00689] Example 312: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (piperidin-1-yl) ethan-1-one

[00690] Example 313: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00691] Example 314: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00692] Example 315: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-

thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (2,2,2-trifluoroethyl) acetamide

[00693] Example 316: (R) -2- (2-methyl-3-thioxo-6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (oxazol-2-yl) acetamide

[00694] Example 317: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (oxazol-2-yl) acetamide

[00695] Example 318: (R) -3- (2-methyl-3-thioxo-6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1- morpholinopropan-1-one

[00696] Example 319: 1- (6,6-dimethyl-3-azabicyclo [3.1.0] hexan-3-yl) -3- ((R) -2-methyl-6- (2,3,5, 6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one

[00697] Example 320: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (piperazin-1-yl) ethan-1-one

[00698] Example 321: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (piperazin-1-yl) ethan-1-one

[00699] Example 322: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -1- (2- (cyclopentylamino) ethyl) -2-methyl-5,5a, 6,6a-tetrahydrocyclopropa [3.4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00700] Example 323: (R) -4- (2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) piperazin-2-one

[00701] Example 324: (R) -1-methyl-4- (2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) piperazin-2-one

[00702] Example 325: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-

methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N - ((1r, 4R) - 4-hydroxycyclohexyl) acetamide

[00703] Example 326: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (4-methylpiperazin-1-yl) ethan-1-one

[00704] Example 327: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[00705] Example 328: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (pyrazin-2-ylmethyl) acetamide

[00706] Example 329: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1-morpholinoetan-1-one

[00707] Example 330: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (cyclopentylamino) ethyl) -2-methyl-5,5a, 6,6a-tetrahydrocyclopropa [3.4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00708] Example 331: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl- 1- (2 - ((((R) -tetrahydro-2H-pyran-3-yl ) amino) ethyl) -5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00709] Example 332: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N- (pyridin-2-ylmethyl) acetamide

[00710] Example 333: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[00711] Example 334: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl- 1- (2 - ((2,2,2-trifluoroethyl) amino) ethyl) -5, 5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00712] Example 335: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-

methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- (pyrazin-2-ylmethyl) acetamide

[00713] Example 336: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((((S) -tetrahydrofuran-2-yl) methyl) acetamide

[00714] Example 337: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((((R) -tetrahydrofuran-2-yl) methyl) acetamide

[00715] Example 338: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - (((1-methyl-1H-pyrazol-4-yl) methyl) acetamide

[00716] Example 339: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - (((1-methyl-1H-pyrazol-4-yl) methyl) acetamide

[00717] Example 340: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (thiazol-2-yl) acetamide

[00718] Example 341: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (cyclohexylamino) ethyl) -2-methyl-5,5a, 6,6a-tetra - hydrocycloprop [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00719] Example 342: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -2-oxopyrrolidin-3-yl) acetamide

[00720] Example 343: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-1- (2 - ((pyridin-2-ylmethyl) amino) ethyl) -5.5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00721] Example 344: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -1 - ((R) -2- (trifluoromethyl) pyrrolidin-1-yl) ethan-1-one

[00722] Example 345: N- (2-cyanocyclopentyl) -2 - ((R) -2-methyl-3-thioxo-6-

(2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00723] Example 346: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-1- (2 - (((1-methyl-1H-pyrazol-4-yl) methyl) amino) ethyl) -5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00724] Example 347: (R) -N- (isoxazol-4-yl) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00725] Example 348: (S) -1- (2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra- hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) pyrrolidine-3-carbonitrile

[00726] Example 349: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (5-methyl-1,3,4-oxadiazol-2-yl) acetamide

[00727] Example 350: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (1-methyl-1H-pyrazol-4-yl) acetamide

[00728] Example 351: (R) -N- (isothiazol-4-yl) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00729] Example 352: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((tetrahydro-2H-pyran-4-yl) methyl) acetamide

[00730] Example 353: 1- (3- (fluoromethyl) pyrrolidin-1-yl) -2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2, 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[00731] Example 354: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -2-oxopiperidin-3-yl) acetamide

[00732] Example 355: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-

methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N - ((1r, 4R) - 4-hydroxycyclohexyl) acetamide

[00733] Example 356: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-cyclohexylacetamide

[00734] Example 357: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N-cyclopropylacetamide

[00735] Example 358: N, N-dimethyl-1- (2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) pyrrolidine-3-carboxamide

[00736] Example 359: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl- 1- (2 - ((((R) -tetrahydrofuran-3-yl) amino) ethyl ) -5.5a, 6.6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[00737] Example 360: 2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00738] Example 361: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocycloprop acid [3, 4] pyrrole [1,2- c] imidazol-1-yl) acetic

[00739] Example 362: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00740] Example 363: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-morpholinoetan-1-one

[00741] Example 364: N-methyl-N- (tetrahydrofuran-3-yl) -2 - ((R) -3-thioxo- 6- (2,3,6-trifluorophenyl) -2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00742] Example 365: N - ((R) -tetrahydro-2H-pyran-3-yl) -2 - ((R) -3-thioxo-6- (2,3,6-trifluorophenyl) -2 , 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-

1-yl) acetamide

[00743] Example 366: (R) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -1-morpholinoetan-1-one

[00744] Example 367: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00745] Example 368: 2 - ((R) -6- (2,3,6-trifluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00746] Example 369: 2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00747] Example 370: 2 - ((R) -6- (2,3,6-trifluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00748] Example 371: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (1-methyl-6-oxopiperidin-3-yl) acetamide

[00749] Example 372: (R) -N-methyl-2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H -pyrrolo [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00750] Example 373: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[00751] Example 374: N-methyl-2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H -pyrrolo [1,2-c] imidazol-1-yl) -N- (tetrahydrofuran-3-yl) acetamide

[00752] Example 375: N-methyl-2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (tetrahydrofuran-3-yl) acetamide

[00753] Example 376: (R) -N- (tetrahydro-2H-pyran-4-yl) -2- (3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00754] Example 377: (R) -N- (tetrahydro-2H-pyran-4-yl) -2- (3-thioxo-6- (2,3,5,6-tetrafluorophenyl) -2,5 , 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00755] Example 378: (R) -N-methyl-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00756] Example 379: (R) -N-methyl-2- (6- (2,3,6-trifluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00757] Example 380: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[00758] Example 381: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[00759] Example 382: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[00760] Example 383: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[00761] Example 384: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[00762] Example 385: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00763] Example 386: N - (((R) -tetrahydro-2H-pyran-3-yl) -2 - ((R) -3-thioxo-6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00764] Example 387: 2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((((S) -tetrahydrofuran-2-yl) methyl) acetamide

[00765] Example 388: N- (1-methyl-2-oxopyrrolidin-3-yl) -2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2 , 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00766] Example 389: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((S) -1-methyl-5-oxopyrrolidin-3-yl) acetamide

[00767] Example 390: (R) -1- (2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra- hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) pyrrolidine-3-carbonitrile

[00768] Example 391: 2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((((R) -tetrahydrofuran-2-yl) methyl) acetamide

[00769] Example 392: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N - ((R) -tetrahydrofuran-3-yl) acetamide

[00770] Example 393: (R) -N- (oxetan-3-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00771] Example 394: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[00772] Example 395: 2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((((S) -tetrahydrofuran-2-yl) methyl) acetamide

[00773] Example 396: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[00774] Example 397: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((tetrahydro-2H-pyran-4-yl) methyl) acetamide

[00775] Example 398: (R) -N-methyl-2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[00776] Example 399: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N - ((R) - tetrahydrofuran-3-yl) acetamide

[00777] Example 400: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrole [1,2- c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[00778] Example 401: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[00779] Example 402: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[00780] Example 403: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrole [1,2- c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[00781] Example 404: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00782] Example 405: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[00783] Example 406: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00784] Example 407: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1, 2-c] imidazol-1-yl) acetic

[00785] Example 408: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[00786] Example 409: (S) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole acid [ 1,2-c] imidazol-1-yl) acetic

[00787] Example 410: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00788] Example 411: (S) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -1-morpholinoetan-1-one

[00789] Example 412: 2 - ((S) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00790] Example 413: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[00791] Example 414: (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[00792] Example 415: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[00793] Example 416: (S) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00794] Example 417: 2 - ((S) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00795] Example 418: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00796] Example 419: (S) -2- (6- (3,5-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-morpholinoetan-1-one

[00797] Example 420: (R) -N-methyl-N- (oxetan-3-yl) -2- (3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[00798] Example 421: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrole [1,2- c] imidazol-1-yl) -1-morpholinoetan-1-one

[00799] Example 422: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -1-morpholinoetan-1-one

[00800] Example 423: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00801] Example 424: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H- acid pyrrole [1,2-c] imidazol-1-yl) acetic

[00802] Example 425: 2 - ((S) -6- (3,5-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00803] Example 426: 2 - ((S) -6- (3,5-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00804] Example 427 (S) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazol-1-yl) -N - (((tetrahydro-2H-pyran-4-yl) methyl) acetamide

[00805] Example 428: (S) -2- (6- (3,5-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - (((tetrahydro-2H-pyran-4-yl) methyl) acetamide

[00806] Example 429: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[00807] Example 430: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N - (((1-methyl-1H-pyrazol-4-yl) methyl) acetamide

[00808] Example 431: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[00809] Example 432: (S) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[00810] Example 433: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[00811] Example 434: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[00812] Example 435: (S) -N-methyl-2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[00813] Example 436: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -1-morpholinoetan-1-one

[00814] Example 437: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[00815] Example 438: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[00816] Example 439: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[00817] Example 440: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[00818] Example 441: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[00819] Example 442: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrole [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[00820] Example 443: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[00821] Example 444: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1- (isoxazolidin-2-yl) ethan-1-one

[00822] Example 445: (R) -2- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-morpholinoetan-1-one

[00823] Example 446: 2 - ((R) -6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00824] Example 447 (R) -2- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2- c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00825] Example 448: (R) -2- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-

2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[00826] Example 449: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((S) -1-methyl-5-oxopyrrolidin-3-yl) acetamide

[00827] Example 450: (S) -1- (2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) pyrrolidine-3-carbonitrile

[00828] Example 451: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N - ((R) - tetrahydrofuran-3-yl) acetamide

[00829] Example 452: (S) -1- (2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) -N, N-dimethylpiperidine-4-carboxamide

[00830] Example 453: 1- (2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) -N, N-dimethylpyrrolidine-3-carboxamide

[00831] Example 454: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[00832] Example 455: N-methyl-2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H -pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) - tetrahydrofuran-3-yl) acetamide

[00833] Example 456: (S) -6- (3-bromo-2,6-difluorophenyl) -1- (2-hydroxyethyl) -2-methyl-2,5,6,7-tetrahydro-3H- pyrrole [1,2-c] imidazole-3-thione

[00834] Example 457: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (1-methyl-6-oxopiperidin-3-yl) acetamide

[00835] Example 458: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1- (3-

(fluoromethyl) pyrrolidin-1-yl) ethan-1-one

[00836] Example 459: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00837] Example 460: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2- (methyl-d3) - 3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) -1- morpholinoetan-1-one

[00838] Example 461: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2- (methyl-d3) -3-thioxo-2,3,5,5a, 6.6a -hexa-hydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[00839] Example 462: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2- (methyl-d3) -3-thioxo-2,3,5,5a, 6.6a -hexa-hydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic acid

[00840] Example 463: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2- (methyl-d3) -3-thioxo-2,3,5,5a, 6.6a -hexa-hydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00841] Example 464: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2- (methyl-d3) -3-thioxo-2,3,5,5a, 6.6a -hexa-hydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[00842] xample 465: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2- (methyl-d3) -3-thioxo-2,3,5,5a, 6,6a -hexa-hydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[00843] Example 466: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N - ((R) -tetrahydrofuran-3-yl) acetamide

[00844] Example 467: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N - ((R) -tetrahydrofuran-3-yl) acetamide

[00845] Example 468: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrole [1,2-

c] imidazol-1-yl) -N-methyl-N - (((R) -tetrahydrofuran-3-yl) acetamide

[00846] Example 469: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2- (methyl-d3) - 3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[00847] Example 470: R) -6- (2,3,6-trifluoropheni) -1- (2 - ((((R) -tetrahydrofuran-3-yl) amino) ethyl) -2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00848] Example 471: (R) -1- (3- (pyrrolidin-1-yl) propyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[00849] Example 472: (R) -1- (3- (isopropylamino) propyl) -6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazole-3-thione

[00850] Example 473: (R) -1- (2 - ((((tetrahydro-2H-pyran-4-yl) methyl) amino) ethyl) -6- (2,3,6-trifluorophenyl) -2 , 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00851] Example 474: (R) -2-methyl-1- (2- (pyrrolidin-1-yl) ethyl) -6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00852] Example 475: (R) -1- (2 - (((((S) -tetrahydrofuran-2-yl) methyl) amino) ethyl) -6- (2,3,6-trifluorophenyl) -2 , 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00853] Example 476: (R) -1- (2- (tert-butylamino) ethyl) -2-methyl-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[00854] Example 477: (R) -2-methyl-1- (2 - ((((tetrahydro-2H-pyran-4-yl) methyl) amino) ethyl) -6- (2,3,6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[00855] Example 478: (R) -1- (3- (pyrrolidin-1-yl) propyl) -6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazole-3-thione C. Compositions

[00856] The compounds of the invention intended for pharmaceutical use can be administered alone or in combination with one or more other compounds of the invention or in combination with one or more other drugs (or as any combination thereof). These will generally be administered as a formulation in combination with one or more pharmaceutically acceptable excipients. Accordingly, the present invention is also directed to a pharmaceutical composition comprising (i) a therapeutically effective amount of a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof; and (ii) a pharmaceutically acceptable excipient.

[00857] Pharmaceutical compositions suitable for the distribution of the compounds of the present invention and methods for their preparation will be readily apparent to those skilled in the art. Such compositions and methods for their preparation can be found, for example, in "Remington’s Pharmaceutical Sciences", 19th Edition (Mack Publishing Company, 1995). D. Methods of Use

[00858] This invention is also directed to compounds of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, for use in therapy, in particular for the treatment of conditions eased by inhibition of DβH outside the CNS.

[00859] This invention is also directed to the use of the compounds of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of conditions alleviated by inhibition of DβH outside the CNS.

[00860] This invention is also directed to a method for treating conditions eased by dopamine beta-hydroxylase inhibition outside the CNS comprising administering a therapeutically effective amount of a compound of formula Ia, as defined in claim 1, or a salt thereof or pharmaceutically acceptable solvate, to a patient in need.

[00861] Conditions eased by DβH inhibition outside the CNS may include, but are not limited to: cardiovascular disorders, such as Angina, Hypertension, Chronic or Congestive Heart Failure, Pulmonary Hypertension (PH) and Pulmonary Arterial Hypertension (PAH).

[00862] Reference is made to the "Guidelines for the diagnosis and treatment of pulmonary hypertension" (European Heart Journal (2009) 30, 2493-2537) for details on the definition, classification and pathology and pathobiological characteristics of PH.

[00863] Typically, pulmonary hypertension is a group of diseases characterized by a progressive increase in pulmonary vascular resistance that leads to right ventricular failure and premature death. This can be defined by an average pulmonary arterial pressure equal to or greater than 25 mmHg at rest.

[00864] PH has been clinically classified by WHO into 5 groups, according to the disease tail, and symptoms may differ, depending on the "group" that caused the disease. However, the "common" symptoms are as follows:  Difficulty breathing or shortness of breath (main symptom)  Fatigue  Dizziness  Swelling in the ankles or legs (edema)  Bluish lips and skin (cyanosis)  Chest pain  Wrist accelerated and palpitations

[00865] A clinical classification of pulmonary hypertension (PH) has been performed and referred to by McLaughlin et al., In "ACCF / AHA 2009 Expert Consensus Document on Pulmonary Hypertension", J Am Coll Cardiol 53, 1573–1619, 2009. PH has been classified as follows:

1. Pulmonary arterial hypertension (PAH)

1.1. idiopathic (IPAH)

1.2 Family member (FPAH)

1.3 Associated with (APAH):

1.3.1 Connective tissue disorder

1.3.2 Systemic-pulmonary congenital shunts

1.3.3 Portal hypertension

1.3.4 HIV infection

1.3.5 Drugs and toxins

1.3.6 Others (thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, chronic myeloproliferative disorders, splenectomy)

1.4 Associated with significant venous or capillary involvement

1.4.1 Veno-occlusive lung disease (PVOD)

1.4.2 Pulmonary capillary hemangiomatosis (PCH)

1.5 Persistent pulmonary hypertension of the newborn

2. Pulmonary hypertension with left heart disease

2.1. Left atrial or ventricular heart disease

2.2. Left heart valve disease

3. Pulmonary hypertension associated with lung diseases and / or hypoxemia

3.1. Chronic obstructive pulmonary disease

3.2. Interstitial lung disease

3.3. Respiratory sleep disorder

3.4. Alveolar hypoventilation disorders

3.5 Chronic high altitude exposure

3.6 Developmental abnormalities

4. Pulmonary hypertension due to chronic thrombotic and / or embolic disease (CTEPH)

4.1. Thromboembolic obstruction of proximal pulmonary arteries

4.2. Thromboembolic obstruction of distal pulmonary arteries

4.3. Non-thrombotic pulmonary embolism (tumor, parasites, foreign material)

5. Miscellaneous

[00866] Sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels (adenopathy, tumor, fibrosing mediastinitis)

[00867] WHO also provided the following classification of functional assessment: Class Functional Symptomatic Profile I Patients with pulmonary hypertension but without limitation of the resulting physical activity. Normal physical activity does not cause dyspnea or fatigue, chest pain, or near syncope II Patients with pulmonary hypertension resulting in a slight limitation of physical activity. These are comfortable at rest. Normal physical activity causes dyspnea or fatigue, chest pain, or near syncope III Patients with pulmonary hypertension resulting in marked limitation of physical activity. These are comfortable at rest. Less than normal activity causes dyspnea or excessive fatigue, chest pain, or nearby syncope

IV Patients with pulmonary hypertension who are unable to perform any physical activity without symptoms. These patients show signs of right heart failure. Dyspnea and / or fatigue may even be present at rest. Discomfort is increased by any physical activity. E. General synthesis methodology

[00868] The methods used for the synthesis of the compounds of the invention are illustrated by the schemes below. The starting materials and reagents used in the preparation of these compounds are available from commercial suppliers or can be prepared by methods obvious to those skilled in the art. To make these diagrams easier to read, the option of incorporating deuterium in certain positions is not shown. Specifically, deuterated products can be produced using specifically deuterated starting materials, including, but not limited to, those used in Examples 1-478.

[00869] The starting material for the compounds of formula If, when R1 = H can generally be synthesized by the method described in Scheme 1 as enriched enanciomers or racemates: Scheme 1 heating

[00870] The starting material for the compounds of formula Ii, when R1 = H can generally be synthesized by the method described in Scheme 2 as enriched enanciomers or racemates:

[00871] Scheme 2

[00872] Compounds of formula If or Ii, with several identities for R6, can generally be synthesized by the methods described in Schemes 3-15 as enriched enanciomers or racemates: Scheme 3

Layout 4

Layout 5

Layout 6

Curtis reaction

Layout 7

[00873] Scheme 8 Oalkyl Scheme 9

Dess-Martin periodinane Dess-Martin periodinane

[00874] Scheme 10

Layout 11

Layout 12

Heteroaryl heteroaryl heteroaryl

Scheme 13 alkyl / cycloalkyl alkyl / cycloalkyl

Scheme 14 Scheme 15

[00875] The compounds in which R1 is C1-C6 alkyl, partially or fully deuterated C1-C6 alkyl or C3-C6 cycloalkyl can be synthesized using an alkyl isothiocyanate as shown in Scheme 16 below: Scheme 16 F. Examples

[00876] All compounds and intermediates were characterized by NMR. The spectra were recorded on a Bruker Avance III 600 MHz spectrometer with solvent used as an internal standard. The 13C spectra were recorded at 150 MHz and the 1H spectra were recorded at 600 MHz. The data are reported in the following order: approximate chemical shift (ppm), number of protons, multiplicity (br, broad; d, doublet; m , multiplet; s, singlet; t, triplet) and coupling constant (Hz).

[00877] Ambient temperature in the following protocols means the temperature ranging from 20 ° C to 25 ° C.

[00878] Example 1: 2- (6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl (S) -ethyl acetate

[00879] Step 1: (E) -1,3-difluoro-5- (2-nitrovinyl) benzene

[00880] To a solution of methanol (72 mL), water (36 mL), and 2.5 M sodium hydroxide (32.4 mL, 81 mmol) was added a solution of 3,5-difluorobenzaldehyde (10 g, 70.4 mmol) and nitromethane (4.36 mL, 81 mmol) in methanol (12.00 mL) dropwise over 30 min at 5 ° C, while the internal temperature was maintained between 5 and 10 ° C with cooling external. The reaction was then stirred in the cold for a further 0.5 and then a solution of cc HCl was added. (11.73 mL, 141 mmol) in water (36 mL), in one part, at 0-10 ° C with stirring. The resulting crystals were collected, washed with water and dried to give the product as a light yellow powder. (Yield: 7.0 g, 54%).

[00881] Step 2: 2- (1- (3,5-difluorophenyl) -2-nitroethyl) (S) - diethyl malonate

[00882] To a stirred solution of (E) -1,3-difluoro-5- (2-nitrovinyl) benzene (7.4 g, 40.0 mmol) in dry tetrahydrofuran (75 mL) was added 4- ((1R) -hydroxy ((4S, 8R) -8-vinylquinuclidin-2-yl) methyl) quinolin-6-ol (0.620 g, 1.999 mmol) at room temperature with stirring, followed by addition of diethyl malonate (9 , 15 mL, 60.0 mmol). The mixture was cooled to -15 to -17 ° C under an inert atmosphere and stirred for 20 h in the cold. Then, the mixture was evaporated to dryness in vacuo and the residue was taken up in dichloromethane (100 ml), washed with 1 M HCl, brine, dried over MgSO4 and filtered on a silica pad. The filtrate was concentrated to 20 ml, and the residue was crystallized in dilution with petroleum ether (about 50 ml). The mixture was further diluted with petroleum ether (120 ml), and aged at 5-10 ° C. The resulting solid was collected, washed with petroleum ether, and dried to give the product as an off-white powder. (Yield: 11.46 g, 83%).

[00883] Step 3: (4S) -ethyl 4- (3,5-difluorophenyl) -2-oxopyrrolidine-3-carboxylate

[00884] To a suspension of 2- (1- (3,5-difluorophenyl) -2-nitroethyl) (S) -diethyl malonate (11 g, 31.9 mmol) in methanol (170 mL) was added chloride nickel (II) hexahydrate (7.57 g, 31.9 mmol) followed by addition of sodium borohydride (9.64 g, 255 mmol) in parts with ice cooling. The mixture was stirred for 6 h at room temperature, then mitigated with ammonium chloride solution (300 ml), diluted with dichloromethane (150 ml), acidified with 6 M HCl to pH = 2, and stirred for 16 h. Then, the mixture was extracted with dichloromethane, the organic phase was dried over MgSO4 and evaporated to dryness to give the product as a light yellow crystalline. (Yield: 8.31 g, 97%).

[00885] Step 4: (4S) -4- (3,5-difluorophenyl) -2-oxopyrrolidine-3-carboxylic acid

[00886] To a stirred solution of 4- (3,5-difluorophenyl) -2-oxopyrrolidine-3-carboxylate (4S) -ethyl (8.3 g, 30.8 mmol) in ethanol (130 mL) was added 1 M sodium hydroxide (37.0 mL, 37.0 mmol). The resulting suspension was stirred for 1 h, the organics were then removed in vacuo, and the residue was dissolved in water (300 ml). The product was crystallized on acidification with 6M HCl. The resulting crystals were collected, washed with cold water and dried under vacuum at 50 ° C to give the product as a beige powder. Yield: 6.0 g, 81%.

[00887] Step 5: (S) -4- (3,5-difluorophenyl) pyrrolidin-2-one Toluene, heating

[00888] A solution of (4S) -4- (3,5-difluorophenyl) -2-oxopyrrolidine-3-carboxylic acid (6.0 g, 24.88 mmol) in toluene (350 mL) was stirred under reflux for 3 h, after which the mixture was evaporated to 30 ml and then diluted with petroleum ether. The resulting crystals were collected, washed with petroleum ether and dried in vacuo to give an off-white powder. Yield: 4.83 g, 98%.

[00889] Step 6: (S) -tert-butyl 4- (3,5-difluorophenyl) -2-oxopyrrolidine-1-carboxylate

[00890] To a stirred solution of (S) -4- (3,5-difluorophenyl) pyrrolidin-2-one (4.8 g, 24.34 mmol) in dry dichloromethane (15 mL) was added at room temperature dicarbonate di-tert-butyl (7.80 g, 36.5 mmol), followed by the addition of N, N-dimethylpyridin-4-amine (2.97 g, 24.34 mmol) and triethylamine (3.32 mL, 23.84 mmol). The mixture was then stirred at room temperature for 3 h and then concentrated in vacuo. Chromatography (petroleum ether - ethyl acetate; 4: 1) gave an oil that was crystallized from petroleum ether (60 mL). The product was isolated as a white powder.

[00891] Yield: 6.24 g, 88%. Step 7: (4S) - tert-butyl 4- (3,5-difluorophenyl) -2-hydroxypyrrolidine-1-carboxylate

[00892] To a stirred solution of (S) -tert-butyl 4- (3,5-difluorophenyl) -2-oxopyrrolidine-1-carboxylate (2.5 g, 8.41 mmol) in dry diethyl ether (37 mL) 65% RED-Al (bis (2-methoxyethoxy) aluminum (III) and sodium hydride) (1.51 mL, 5.05 mmol) in toluene at 0-5 ° C was added dropwise under nitrogen and the mixture was stirred for 1 h in the cold. After that, the mixture was blended with sodium bicarbonate solution and stirred for 30 min. The organic phase was dried over MgSO4, and evaporated to dryness to give the product as a yellowish oil. (Yield: 2.56 g, 92%).

[00893] Step 8: (4S) -tert-butyl 2-cyano-4- (3,5-difluorophenyl) pyrrolidine-1-carboxylate

[00894] To a stirred solution of 4- (3,5-difluorophenyl) -2-hydroxypyrrolidine-1-carboxylate (4S) -tert-butyl (3.5 g, 11.69 mmol) in dry dichloromethane (75 mL ) trimethylsilanocarbonitrile (3.14 ml, 23.39 mmol) was added, followed by addition of boron trifluoride etherate (3.26 ml, 25.7 mmol) at -70 ° C. The mixture was stirred for 4 h in the cold, after which it was mitigated with sodium bicarbonate solution and then allowed to warm with stirring to room temperature. The organic phase was dried over MgSO4, filtered and evaporated to dryness in vacuo. Chromatography (petroleum ether - ethyl acetate; 9: 1) gave the compound as a colorless oil. (Yield: 2.43 g, 67%).

[00895] Step 9: (4S) -1- (tert-butoxycarbonyl) -4- (3,5-difluorophenyl) pyrrolidine-2-carboxylic acid

[00896] To a stirred solution of (4S) -tert-butyl 2-cyano-4- (3,5-difluorophenyl) pyrrolidine-1-carboxylate (2.25 g, 7.30 mmol) in ethanol (25 mL ) 3 M sodium hydroxide (12.16 mL, 36.5 mmol) was added and the solution was gently refluxed (oil bath at 80 ° C) for 3 h. After that, ethanol was removed in vacuo and the residue was diluted with water (30 ml) and then acidified with 2 M HCl to pH = 2 at 10-15 ° C. The mixture was extracted with dichloromethane (50 ml), the materials insoluble in both phases were removed by filtration, in which the organic phase was washed with saline, dried over MgSO4 and evaporated to dryness to give 0.90 g of foam. yellowish. (Yield: 37%).

[00897] Step 10: (4S) 4- (3,5-difluorophenyl) -2- (2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-carbonyl) pyrrolidine-1-carboxylate -tert-butyl

[00898] To a solution of (4S) -1- (tert-butoxycarbonyl) -4- (3,5-difluorophenyl) pyrrolidine-2-carboxylic acid (0.35 g, 1.069 mmol), 2,2-dimethyl- 1,3-dioxane-4,6-dione (0.154 g, 1.069 mmol) and N, N-dimethylpyridin-4-amine (0.131 g, 1.069 mmol) were added dropwise dicyclohexylmethanediimine (0.221 g, 1.069 mmol) at 0-5 ° C and the mixture was stirred in the cold for 2 h. The mixture was then filtered through a plug, celite, the filtrate was washed with 1 M HCl, brine, dried over MgSO4 and then evaporated to dryness to give the product as an oil. (Yield: 0.42 g, 87%).

[00899] Step 11: (4S) -tert-butyl 4- (3,5-difluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) pyrrolidine-1-carboxylate

[00900] A solution of 4- (3,5-difluorophenyl) -2- (2,2-dimethyl-4,6-dioxo- 1,3-dioxane-5-carbonyl) pyrrolidine-1-carboxylate (4S) -tert-butyl (0.41 g, 0.904 mmol) in abs ethanol. (5 ml) was stirred at reflux for 3 h. The solvent was then removed in vacuo and the residue was subjected to chromatography (petroleum ether - ethyl acetate; 9: 1). The product was isolated as a colorless oil. (Yield: 0.124 g, 34%).

[00901] Step 12: 2- (6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl ((S) -ethyl acetate

[00902] A solution of 4- (3,5-difluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) pyrrolidine-1-carboxylate (4S) -tert-butyl (0.11 g, 0.277 mmol) in 2M HCl (1.107 mL, 2.214 mmol) in diethyl ether was stirred at room temperature for 5 h and then the solvent was removed in vacuo. The residue was dissolved in a mixture of ethanol (1.5 ml) and water (1.5 ml), treated with potassium thiocyanate (0.030 g, 0.304 mmol) followed by the addition of 6 N HCl (0.023 ml, 0.138 mmol) and then the mixture was stirred at 90 ° C for 3 h. After that, the ethanol was removed in vacuo, and the residue was extracted with a mixture of ethyl acetate - petroleum ether (2: 1). The organic phase was dried over MgSO4, evaporated to dryness and the residue was subjected to chromatography (petroleum ether - EtOAc; 1: 1, then 1: 2). The product was isolated as a light yellow powder.

[00903] (Yield: 0.038 g, 40%).

[00904] 1H NMR (DMSOd6): 11.78 (1 H, s), 7.13 (3 H, m), 4.17 (1 H, dd, J = 11.1, 7.8 Hz) , 4.09 (2 H, q, J = 7.0 Hz), 4.09 (1H, m), 3.70 (1 H, dd, J = 11.2, 7.8 Hz), 3, 52 (2 H, m, J = 3.1 Hz), 3.20 (1 H, dd, J = 15.4, 7.9 Hz), 2.84 (1 H, dd, J = 15.4 , 8.4 Hz), 1.19 (3 H, t, J = 7.1 Hz). 13

[00905] C NMR (DMSOd6): 169.2, 163.3, 163.2, 161.7, 161.6, 155.6, 145.8, 145.8, 145.7, 129.9, 113, 110.7, 110.7, 110.6, 110.6, 102.7, 102.5, 102.3, 60.7, 50.3, 46.4, 30.4, 29.8, 14.1.

[00906] Example 2: 2- (6- (2,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl ) (S) -ethyl acetate and

[00907] Example 3: (S) -2- (6- (2,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [1,2-c] imidazol-1-yl) acetic

[00908] Step 1: tert-Butyl (4S) -4- (2,5-difluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) pyrrolidine-1-carboxylate

[00909] A mixture of potassium 3-ethoxy-3-oxopropanoate (0.741 g, 4.35 mmol) and magnesium bromide diethyl ether (0.749 g, 2.90 mmol) in dry tetrahydrofuran (10 mL) was stirred under inert atmosphere at 50 ° C for 6 h. In parallel, di (1H-imidazol-1-yl) methanone (0.706 g, 4.35 mmol) was added in parts to a solution of (4S) -1- (tert-butoxycarbonyl) -4- (2.5 -difluorophenyl) pyrrolidine-2-carboxylic (prepared analogously to Example 1, step 9) (0.95 g, 2.90 mmol) in dry tetrahydrofuran (8.00 mL) at 0-5 ° C and at The mixture was stirred for 2 h at room temperature. The solution was then added to the first suspension dropwise and the mixture was stirred for 16 h at room temperature. After that, the mixture was mitigated with aq. of NaHSO4 and then extracted with a mixture of ethyl acetate - petroleum ether (2: 1). The organic phase was washed with sodium bicarbonate, dried over MgSO4 and evaporated to dryness. Chromatography on a mixture of petroleum ether - ethyl acetate (9: 1) gave (4S) -tert-butyl 4- (2,5-difluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) pyrrolidine-1 -carboxylate. (Yield: 0.56 g, 48.6%).

[00910] Step 2: 2- (6- (2,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl ) (S) -ethyl acetate and (S) -2- (6- (2,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [1,2 -c] imidazol-1-yl) acetic

[00911] A solution of 4- (2,5-difluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) pyrrolidine-1-carboxylate (4S) -tert-butyl (0.56 g, 1.409 mmol) in 2 M HCl (5.64 ml, 11.27 mmol) in diethyl ether was stirred at room temperature for 16 h, in which the solvent was removed in vacuo, and the residue was dissolved in a mixture of ethanol (6 ml) and water (6 mL). The reaction mixture was treated with potassium thiocyanate (0.151 g, 1.550 mmol) followed by addition of 6 M HCl (0.117 mL, 0.705 mmol) and then stirred for 2 h. After that, the ethanol was removed in vacuo, where the resulting solid was collected and washed with water. The precipitate was dissolved in ethyl ethyl acetate, dried over MgSO4, filtered through a pad of silica and then evaporated to dryness. Crystallization from petroleum ether gave 2- (6- (2,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2- c] imidazole- 1-yl) (S) -ethyl acetate as an off-white powder. (Yield: 0.19 g, 39%).

[00912] 1H NMR (DMSOd6): 11.79 (1 H, br s), 7.27 (2 H, m), 7.18 (1 H, m), 4.23 (1 H, quin, J = 7.7 Hz), 4.15 (1 H, dd, J = 11.2, 8.0 Hz), 4.09 (2 H, q, J = 7.1 Hz), 3.75 ( 1 H, dd, J = 11.2, 7.5 Hz), 3.52 (2 H, m), 3.22 (1 H, dd, J = 15.5, 8.0 Hz), 2, 87 (1 H, br dd, J = 15.6, 7.8 Hz), 1.19 (3 H, t, J = 7.0 Hz). 13

[00913] C NMR (DMSOd6): 169.2, 159, 157.5, 157.1, 155.6, 155.5, 130.1, 130, 130, 129.9, 129.8, 117, 2, 117.1, 117, 116.9, 115.5, 115.4, 115.3, 115.3, 115.2, 115.2, 115.1, 115, 113, 60.7, 49, 4, 40.3, 29.8, 29.6, 14.1.

[00914] The aqueous mother liquor from the above procedure was extracted with dichloromethane. The organic phase was extracted with aq. NaOH, then the aqueous phase was acidified and extracted with dichloromethane. The organic phase was dried over MgSO4, evaporated to dryness to give 67 mg (15% yield) of (S) -2- (6- (2,5-difluorophenyl) -3-thioxo-3,5,6 acid, 7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) acetic as an off-white powder.

[00915] 1H NMR (DMSOd6): 12.58 (1 H, br s), 11.75 (1 H, s), 7.28 (2 H, m), 7.18 (1 H, m) , 4.22 (1 H, quin, J = 7.8 Hz), 4.14 (1 H, dd, J = 11.2, 7.9 Hz), 3.73 (1 H, dd, J = 11.3, 7.3 Hz), 3.43 (2 H, m), 3.21 (1 H, dd, J = 15.5, 8.0 Hz), 2.87 (1 H, dd, J = 15.4, 7.8 Hz). 13

[00916] C NMR (DMSOd6): 170.8, 159.1, 157.5, 157.1, 155.5, 155.5, 130.1, 130, 130, 129.9, 129.5, 117.1, 117.1, 117, 116.9, 115.5, 115.4, 115.3, 115.3, 115.2, 115.1, 115.1, 113.8, 49.4, 40.3, 30, 29.5.

[00917] Example 4: 2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) methyl acetate

[00918] Step 1: ((1R, 2S) -2- (aminomethyl) -2- (2,5-difluorophenyl) cyclopropyl) methanol

[00919] To a stirred solution of 2- (2,5-difluorophenyl) acetonitrile (10.0 g, 65.3 mmol) in dry tetrahydrofuran (100 mL), was added (R) -2- (chloromethyl) oxirane (6.13 mL, 78.0 mmol) at room temperature, under nitrogen. The reaction was then cooled to 15 ° C and 2 M sodium bis (trimethylsilyl) amide in tetrahydrofuran (57.1 ml, 114.0 mmol) was added dropwise at 15 ° C over a period of 2 H. Thereafter, the red mixture thus obtained was allowed to warm to room temperature and stirred for 3 h. The reaction was diluted with dry tetrahydrofuran (100 ml), cooled to 0 ° C and then sodium borohydride (9.88 g, 261 mmol) was added followed by dropwise addition of etherate boron trifluoride (33.10 mL, 261 mmol). The mixture was allowed to warm to room temperature and stirred overnight. The resulting pale yellow suspension was cooled to 0 ° C and carefully mitigated with 2M HCl (196 ml, 392 mmol). The tetrahydrofuran was then removed by evaporation and the aqueous phase was washed with diethyl ether. The pH of the aqueous phase was set to pH = 10 by adding 3 M sodium hydroxide and then extracted with dichloromethane. The organic phase was dried over MgSO4, filtered and evaporated to dryness in vacuo to leave a yellow oil.

[00920] (Yield: 12.91 g, 74%).

[00921] Step 2: tert-butyl ((((1S, 2R) -1- (2,5-difluorophenyl) -2- (hydroxymethyl) cyclopropyl) methyl) carbamate

[00922] To an ice-cold solution of ((1R, 2S) -2- (aminomethyl) -2- (2,5-difluorophenyl) cyclopropyl) methanol (12.91 g, 60.5 mmol) in ethanol (207 mL) di-tert-butyl dicarbonate (13.21 g, 60.5 mmol) was added. The solution was stirred at room temperature for 3 h and then the solvent was removed by evaporation in vacuo. The resulting yellow oil was purified by chromatography (petroleum ether - ethyl acetate). The product was isolated as a white powder. (Yield: 14.28 g, 64%).

[00923] Step 3: tert-Butyl (1S, 5R) -1- (2,5-difluorophenyl) -4-hydroxy-3-azabicyclo [3.1.0] hexane-3-carboxylate

[00924] To a stirred solution of oxalyl dichloride (4.39 mL, 50.10 mmol) in dry dichloromethane (120 mL), a solution of dimethylsulfoxide (4.12 mL, 100.0) was added dropwise mmol) in dry dichloromethane (22 mL) at -78 ° C. The reaction mixture was stirred in the cold for 15 min and then a solution of (((1S, 2R) -1- (2,5-difluorophenyl) -2- (hydroxymethyl) cyclopropyl) was added dropwise tert-butyl methyl) carbamate (14.28 g, 45.60 mmol) in dry dichloromethane (44 mL). The mixture was stirred at - 78 ° C for 1 h and then triethylamine (31.8 ml, 228.0 mmol) was added. The reaction was allowed to gradually warm to room temperature and stirred at room temperature for 2 h. After that, the mixture was washed three times with water, dried over MgSO4, filtered and evaporated to dryness to give a yellow oil. (Yield: 14.5 g, ≈100%).

[00925] Step 4: tert-Butyl (1S, 5R) -4-cyano-1- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate

[00926] To a stirred solution of tert-butyl (1S, 5R) -1- (2,5-difluorophenyl) -4-hydroxy-3-azabicyclo [3.1.0] hexane-3-carboxylate (14.2 g , 45.60 mmol) in dry dichloromethane (230 mL) trimethylsilanocarbonitrile (16.33 mL, 122.0 mmol) was added at room temperature under nitrogen. The solution was then cooled to -78 ° C and boron trifluoride (16.83 ml, 134.0 mmol) was added dropwise. The reaction mixture was stirred in the cold for 4 h and then saturated sodium bicarbonate solution was added and allowed to warm to room temperature. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried over MgSO4, filtered and evaporated to dryness to leave a yellow oil. (Yield: 14.9 g, 92%).

[00927] Step 5: (1R, 5S) -3- (tert-butoxycarbonyl) -5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-2-carboxylic

[00928] To a stirred solution of tert-butyl (1S, 5R) -4-cyano-1- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (14.61 g , 45.6 mmol) in ethanol (145 mL), a 3 M sodium hydroxide solution (76 mL, 228.0 mmol) was added at room temperature. The solution was heated to 80 ° C for 4 h and then cooled to room temperature. After that, the ethanol was removed by evaporation and the aqueous phase was acidified with 2 M HCl solution and then extracted with a mixture of dichloromethane - isopropanol (7: 3). The organic phase was dried over MgSO4, filtered and evaporated to dryness to leave a yellow oil, which solidified on standing.

[00929] (Yield: 17.0 g, 93%).

[00930] Step 6: 1- (2,5-difluorophenyl) -4- (2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-carbonyl) -3-azabicycle [3.1.0] (1S, 5R) - tert-butyl hexane-3-carboxylate

[00931] To a stirred solution of (1R, 5S) -3- (tert-

butoxycarbonyl) -5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-2-carboxylic (2.5 g, 7.37 mmol) in dichloromethane (50 mL) 2,2-dimethyl was added -1,3-dioxane-4,6-dione (1.062 g, 7.37 mmol) at room temperature followed by the addition of N, N-dimethylpyridin-4-amine (0.900 g, 7.37 mmol). The solution thus obtained was cooled to 0 ° C and a solution of N, N'-dicyclohexylcarbodiimide (1.520 g, 7.37 mmol) in dichloromethane was added dropwise. The mixture was stirred in the cold for 2 h and then filtered through a pad of celite. The filtrate was washed with 1 M HCl and brine, dried over MgSO4, filtered and evaporated to dryness to give a yellow semi-solid. Yield: 3.45 g, 100%.

[00932] Step 7: 1- (2,5-difluorophenyl) -4- (3-methoxy-3-oxopropanoyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (1S, 5R) -tert- butyl

[00933] A solution of 1- (2,5-difluorophenyl) -4- (2,2-dimethyl-4,6-dioxo- 1,3-dioxane-5-carbonyl) -3-azabicyclo [3.1.0] (1S, 5R) -tert-butyl hexane-3-carboxylate (3.43 g, 7.37 mmol) in dry methanol (40 mL), was heated to reflux for 3.5 h under inert atmosphere. The solution was then cooled to room temperature and the solvent was removed by evaporation. The resulting yellow oil was purified by chromatography (petroleum ether - ethyl acetate; 9/1, 4/1, 2/1, then 1/1). The product was isolated as a colorless oil. (Yield: 1.84 g, 53%).

[00934] Step 8: methyl 3 - ((1R, 5S) -5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexan-2-yl) -3-oxopropanoate hydrochloride

[00935] 1- (2,5-Difluorophenyl) -4- (3-methoxy-3-oxopropanoyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate of (1S, 5R) -tert-butyl (1 , 79 g, 4.53 mmol) was stirred in 2 M ethereal HCl solution (18.11 mL, 36.2 mmol) for 8 h. After that, the reaction mixture was evaporated to dryness to leave the product as a white foam. (Yield: 1.14 g, 76%).

[00936] Step 9: 2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) methyl acetate

[00937] To a stirred solution of methyl 3 - ((1R, 5S) -5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexan-2-yl) -3-oxopropanoate ( 1.14 g, 3.44 mmol) in a mixture of ethanol (14 mL) and water (14 mL) was added potassium thiocyanate (0.367 g, 3.78 mmol) followed by addition of cc HCl. (0.14 mL, 1.718 mmol). The solution was heated to reflux for 5 h, then cooled to room temperature and evaporated to dryness. The resulting oil was extracted from the aqueous phase with dichloromethane. The organic phase was dried over MgSO4, filtered and evaporated to dryness. The yellow oil thus obtained was separated by chromatography (dichloromethane - methanol; 98: 2, then 95: 5), then chromatographed again (petroleum ether - ethyl acetate; 1: 1,

then 1: 2). The product was isolated as a yellow solid. (Yield: 90 mg, 7%).

[00938] 1H NMR (DMSOd6): 11.73 (1 H, s), 7.29 (1 H, m), 7.26 (1 H, m), 7.21 (1 H, m), 4.10 (1 H, br d, J = 12.3 Hz), 3.82 (1 H, d, J = 12.0 Hz), 3.66 (3 H, s), 3.59 (2 H, m), 2.87 (1 H, dd, J = 8.2, 4.3 Hz), 1.67 (1 H, dd, J = 8.2, 5.4 Hz), 1.14 (1 H, br t, J = 4.7 Hz). 13

[00939] C NMR (DMSOd6): 169.7, 158.8, 158.6, 157.2, 157, 156.3, 132.3, 128.6, 128.5, 128.4, 117, 2, 117.1, 117, 117, 116.8, 116.8, 116, 115.9, 115.8, 115.7, 112.2, 52, 51.6, 51.5, 32.5, 29.6, 22.2, 20.7.

[00940] Example 5: 2 - ((5aS, 6aR) -5a- (3,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) methyl acetate.

[00941] (1R, 5S) -3- (tert-butoxycarbonyl) -5- (3,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-2-carboxylic acid was converted to 2 - ((5aS, 6aR) - 5a- (3,5-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl ) methyl acetate using a procedure similar to that described for Example 4 and the product was isolated as a yellow solid.

[00942] 1H NMR (DMSOd6): 11.72 (1 H, s), 7.11 (3 H, m), 4.20 (1 H, d, J = 12.0 Hz), 4.06 (1 H, d, J = 12.2 Hz), 3.65 (3 H, s), 3.57 (2 H, m), 2.97 (1 H, dd, J = 8.2, 4 , 4 Hz), 1.70 (1 H, dd, J = 8.2, 5.3 Hz), 1.16 (1 H, t, J = 4.8 Hz). 13

[00943] C NMR (DMSOd6): 169.7, 163.4, 163.3, 161.8, 161.7, 156.5, 144.8, 144.7, 144.7, 132.3, 112, 110, 110, 109.9, 109.8, 102.3,

102.1, 102, 52, 50.7, 36.2, 29.6, 25.2, 22.9.

[00944] Example 6: 2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa acid [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic

[00945] To a stirred solution of 2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2- c] imidazol-1-yl) ethyl acetate (prepared analogously to Example 4) (275 mg, 0.785 mmol) in ethanol (3 ml) 1 M sodium hydroxide (0.942 ml , 0.942 mmol) at room temperature and the solution was stirred for 2 h. After that, a second crop of 1 M sodium hydroxide (0.942 ml, 0.942 mmol) was added and the reaction was allowed to stir for an additional 1 h. Ethanol was then removed in vacuo and the aqueous phase was extracted with dichloromethane. The aqueous phase was acidified to pH = 1 by adding aqueous HCL solution and then extracted with dichloromethane. The organic phase was evaporated to dryness to give the product as a yellow foam. (Yield: 0.206 g, 76%).

[00946] 1H NMR (DMSOd6): 12.57 (1 H, br s), 11.70 (1 H, s), 7.29 (1 H, td, J = 9.4, 4.6 Hz ), 7.25 (1 H, ddd, J = 9.1, 5.9, 3.2 Hz), 7.21 (1 H, m), 4.09 (1 H, d, J = 11, 9 Hz), 3.81 (1 H, d, J = 12.0 Hz), 3.47 (2 H, m), 2.87 (1 H, dd, J = 8.4, 4.3 Hz ), 1.66 (1 H, dd, J = 8.4, 5.3 Hz), 1.13 (1 H, t, J = 4.8 Hz).

[00947] 13C NMR (DMSOd6): 170.7, 158.8, 158.6, 157.2, 157, 157, 156.1, 132.1, 128.6, 128.6, 128.5, 128.5, 117.2, 117.1, 117, 117, 116.9,

116.8, 116.8, 115.9, 115.9, 115.8, 115.7, 113, 51.6, 51.5, 32.5, 29.9, 22.3, 20.7.

[00948] Example 7: 2 - ((5aS, 6aR) -5a- (3,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa acid [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic.

[00949] The compound was prepared using a similar procedure as described for Example 6 and the product was isolated as a yellow solid.

[00950] 1H NMR (DMSOd6): 12.60 (1 H, br s), 11.69 (1 H, s), 7.10 (3 H, m), 4.20 (1 H, d, J = 12.2 Hz), 4.05 (1 H, d, J = 12.2 Hz), 3.45 (2 H, m), 2.98 (1 H, dd, J = 8.3, 4.3 Hz), 1.70 (1 H, dd, J = 8.3, 5.4 Hz), 1.16 (1 H, t, J = 4.8 Hz). 13

[00951] C NMR (DMSOd6): 170.7, 163.4, 163.3, 161.8, 161.7, 156.3, 144.9, 144.8, 144.7, 132, 112, 8, 110, 110, 109.8, 109.8, 102.3, 102.1, 101.9, 50.7, 36.2, 29.9, 25.3, 22.9.

[00952] Example 8: (5aS, 6aR) -5a- (3,5-difluorophenyl) -1- (2-hydroxyethyl) - 5.5a, 6.6a-tetrahydrocyclopropa [3,4] pyrrole [1, 2-c] imidazole-3 (2H) -thione

[00953] To a stirred solution of 2 - ((5aS, 6aR) -5a- (3,5-

difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) ethyl acetate (300 mg, 0.856 mmol ) (analogous to Example 5) in a methanol mixture abs. (2.3 ml) and dry tetrahydrofuran (2.3 ml) lithium chloride (0.061 ml, 3.00 mmol) was added. The reaction mixture was then cooled to 0 ° C and sodium borohydride (113 mg, 3.00 mmol) was added in parts. The white suspension thus obtained was warmed to room temperature and stirred for 24 h. After that, water was added and the mixture was extracted with dichloromethane. The organic phase was dried over MgSO4, filtered and evaporated to dryness to leave a yellow oil. Chromatography (petroleum ether - ethyl acetate; 1: 1, 1: 4, then 5% methanol in dichloromethane) followed by trituration with heptane gave the product as a light yellow solid. (Yield: 0.065 g, 23%).

[00954] 1H NMR (DMSOd6): 11.64 (1 H, s), 7.10 (3 H, m), 4.74 (1 H, t, J = 5.4 Hz), 4.17 (1 H, d, J = 12.0 Hz), 4.02 (1 H, d, J = 12.0 Hz), 3.59 (2 H, m), 2.98 (1 H, dd, J = 8.2, 4.3 Hz), 2.53 (2 H, td, J = 6.8, 2.9 Hz), 1.65 (1 H, dd, J = 8.1, 5, 2 Hz), 1.16 (1 H, t, J = 4.8 Hz). 13

[00955] C NMR (DMSOd6): 163.4, 163.3, 161.8, 161.7, 155.9, 145.1, 145.1, 145, 130.9, 116.8, 109, 9, 109.9, 109.8, 109.8, 102.2, 102, 101.9, 59.4, 50.5, 36, 28, 25.6, 22.9. Example 9: (S) -2- (6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole-1- il) -1-morpholinoethanone

[00956] Step 1: (4S) -tert-butyl 4- (3,5-difluorophenyl) -2- (3-morpholino-3-oxopropanoyl) pyrrolidine-1-carboxylate

[00957] A mixture of 4- (3,5-difluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) pyrrolidine-1-carboxylate (4S) -tert-butyl (prepared according to the protocol of Example 2 , Step 1) (0.74 g, 1.862 mmol), morpholine (0.324 mL, 3.72 mmol) and N, N-dimethylpyridin-4-amine (0.068 g, 0.559 mmol) in toluene (3 mL) was stirred at 100 ° C for 20 h. The reaction was then diluted with a mixture of ethyl acetate - petroleum ether (1: 1) and washed with 1M HCl. The organic phase was dried over MgSO4, desorbed to dryness and purified by chromatography on a mixture of acetate. ethyl - petroleum ether (1: 1) to give 4- (3,5-difluorophenyl) -2- (4S) -tert-butyl 4- (3,5-morpholino-3-oxopropanoyl) pyrrolidine-1-carboxylate. Yield: 0.634 g, 78%.

[00958] Step 2: (1 - ((4S) -4- (3,5-difluorophenyl) pyrrolidin-2-yl) -3-morpholinopropane-1,3-dione hydrochloride

[00959] A solution of 4- (2,5-difluorophenyl) -2- (3-morpholino-3-oxopropanoyl) pyrrolidine-1-carboxylate (4S) -tert-butyl (0.66 g, 1.505 mmol) in 4M HCl (7.53 mL, 30.1 mmol) in dioxane was stirred for 4 h at room temperature. After that, the reaction mixture was diluted with diethyl ether, the resulting solid was collected, washed with diethyl ether and petroleum ether, respectively and then vacuum dried at 50 ° C to give 1 - ((4S) -4 hydrochloride - (3,5-difluorophenyl) pyrrolidin-2-yl) - 3-morpholinopropane-1,3-dione as a white powder. Yield: 0.52 g, 92%.

[00960] Step 3: (S) -2- (6- (3,5-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazole -1-yl) -1-morpholinoetan-1-one

[00961] A hydrochloride solution of 1 - ((4S) -4- (3,5-difluorophenyl) pyrrolidin-2-yl) -3-morpholinopropane-1,3-dione (0.52 g, 1.387 mmol), potassium thiocyanate (0.148 g, 1.526 mmol) and 6 M HCl (0.12 mL, 0.69 mmol) in a mixture of ethanol (7 mL) and water (7.00 mL) was stirred under reflux for 1 h. the ethanol was evaporated in vacuo. The aqueous phase was extracted with ethyl acetate, the organic phase was diluted with petroleum ether without drying until crystallization occurred. The resulting solid was collected and recrystallized from a mixture of DCM - petroleum ether to give (S) -2- (6- (3,5-difluorophenyl) -3-thioxo- 3,5,6,7-tetra -hydro-2H-pyrrolo [1,2-c] imidazol-1-yl) -1-morpholinoethanone as a white powder. (Yield: 0.051 g, 9%.)

[00962] 1H NMR (DMSOd6): 11.66 (1 H, s), 7.12 (3 H, br d, J = 8.2 Hz), 4.16 (1 H, dd, J = 11 , 1, 7.8 Hz), 4.07 (1 H, quin, J = 7.8 Hz), 3.69 (1 H, dd, J = 11.1, 7.8 Hz), 3.56 (4 H, m), 3.52 (2 H, s), 3.46 (4 H, m), 3.15 (1 H, br dd, J = 15.2, 7.8 Hz), 2 , 80 (1 H, br dd, J = 15.3, 8.2 Hz). 13

[00963] C NMR (DMSOd6): 166.9, 163.3, 163.2, 161.7, 161.6, 155.4, 145.9, 145.8, 145.8, 129.4, 114.4, 110.7, 110.7, 110.6, 110.6, 102.6, 102.5, 102.3, 66, 50.2, 46.4, 45.7, 41.7, 30.5, 28.8.

[00964] Example 10: (S) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo- 3,5,6,7-tetrahydro-2H-pyrrole [1,2 -c] imidazol-1-yl) acetic acid

[00965] The compound was prepared in an analogous manner to Example 3 from (4S) -1- (tert-butoxycarbonyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-2-carboxylic acid and isolated as a whitish powder.

[00966] 1H NMR (DMSOd6): 12.58 (1 H, m), 11.79 (1 H, s), 7.85 (1 H, m), 4.50 (1 H, quin, J = 8.5 Hz), 4.18 (1 H, dd, J = 11.6, 9.2 Hz), 3.78 (1 H, dd, J = 11.7, 7.8 Hz), 3 , 41 (2 H, s), 3.30 (1 H, br dd, J = 15.9, 9.3 Hz), 2.91 (1 H, dd, J = 15.9, 8.0 Hz ). 13

[00967] C NMR (DMSOd6): 170.7, 155.3, 146.4, 145.3, 144.7, 143.7, 129.4, 120.5, 120.4, 120.3, 113.5, 105.9, 105.7, 105.6, 48.5, 35.7, 30, 29.1.

[00968] Example 11: (S) -2- (6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [1,2-c] imidazol-1-yl) acetic

[00969] The compound was prepared analogously to Example 3 from 4- (3,5-difluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) (4S) -tert-butyl-pyrrolidine-1-carboxylate and isolated as a whitish powder.

[00970] 1H NMR (DMSOd6): 12.58 (1 H, br s), 11.74 (1 H, br s), 7.13 (3 H, m), 4.16 (1 H, dd , J = 11.2, 7.9 Hz), 4.08 (1 H, quin, J = 8.0 Hz),

3.70 (1 H, dd, J = 11.2, 7.8 Hz), 3.42 (2 H, m), 3.20 (1 H, dd, J = 15.4, 7.8 Hz ), 2.85 (1 H, dd, J = 15.4, 8.4 Hz). 13

[00971] C NMR (DMSOd6): 170.7, 163.3, 163.2, 161.7, 161.6, 155.5, 145.9, 145.8, 145.7, 129.7, 113.6, 110.8, 110.7, 110.6, 110.6, 102.7, 102.5, 102.3, 50.3, 46.4, 30.4, 29.9.

[00972] Example 12: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1, 2-c] imidazol-1-yl) acetic

[00973] The compound was prepared analogously to Example 3 from 4- (3-bromo-2,6-difluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) pyrrolidine-1-carboxylate (4S) -tert-butyl and isolated as a yellowish solid.

[00974] 1H NMR (DMSOd6): 12.56 (2 H, m), 11.78 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8 , 8 Hz), 7.16 (1 H, dt, J = 1.4, 9.4 Hz), 4.46 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.5, 9.3 Hz), 3.73 (1 H, dd, J = 11.6, 7.9 Hz), 3.41 (2 H, s), 3.26 (1 H, dd, J = 15.8, 9.3 Hz), 2.86 (1 H, dd, J = 15.8, 8.1 Hz). 13

[00975] C NMR (DMSOd6): 170.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.3, 132.5, 132.4, 129.6, 118.8, 118.7, 118.5, 113.8, 113.8, 113.7, 113.6, 113.4, 104.1, 104, 1, 103.9, 103.9, 48.7, 35.6, 29.9, 29.2. Example 13: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) acetic

[00976] The compound was prepared analogously to Example 3 from 4- (3-bromo-2,6-difluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) (4R) pyrrolidine-1-carboxylate -tert-butyl and isolated as a yellowish solid.

[00977] 1H NMR (DMSOd6): 12.56 (1 H, br s), 11.78 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.17 (1 H, dt, J = 1.4, 9.6 Hz), 4.46 (1 H, quin, J = 8.6 Hz), 4.16 (1 H , dd, J = 11.4, 9.3 Hz), 3.73 (1 H, dd, J = 11.7, 8.0 Hz), 3.41 (2 H, m), 3.26 ( 1 H, dd, J = 15.8, 9.4 Hz), 2.86 (1 H, dd, J = 15.8, 8.2 Hz). 13

[00978] C NMR (DMSOd6): 170.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.3, 132.5, 132.4, 129.6, 118.8, 118.7, 118.5, 113.8, 113.8, 113.7, 113.6, 113.3, 104.1, 104, 1, 103.9, 103.9, 48.7, 35.6, 29.9, 29.2.

[00979] Example 14: (R) -2- (6- (2,5-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1,2-c] imidazol-1-yl) acetic

[00980] The compound was prepared in an analogous manner to Example 3 from 4- (2,5-difluorophenyl) -2- (4R) -tert-butyl 4- (2,5-ethoxy-3-oxopropanoyl) pyrrolidine-1-carboxylate and isolated as a pale yellow solid.

[00981] 1H NMR (DMSOd6): 12.60 (1 H, s br), 11.78 (1 H, s), 7.32- 7.26 (2 H, m), 7.18 (1 H, m), 4.22 (1 H, quin, J = 7.8 Hz), 4.14 (1 H, dd, J = 11.3, 7.9 Hz), 3.73 (1 H, dd, J = 11.3, 7.5 Hz), 3.40 (2 H, m), 3.21 (1 H, dd, J = 15.5, 8.0 Hz), 2.86 (1 H, dd, J = 15.5, 7.8 Hz). 13

[00982] C NMR (DMSOd6): 170.8, 159.1, 159.1, 157.5, 157.5, 157.1, 157.1, 155.5, 155.5, 155.5, 130.1, 130.1, 130, 130, 129.5, 117.2, 117.1, 117, 116.9, 115.5, 115.4, 115.3, 115.3, 115.2, 115.1, 115.1, 113.8, 49.4, 40.3, 30, 29.5.

[00983] Example 15: (R) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1, 2-c] imidazol-1-yl) acetic

[00984] The compound was prepared analogously to Example 3 from 4- (2,3,5,6-tetrafluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) (4R) pyrrolidine-1-carboxylate -tert-butyl and isolated as a light cream powder.

[00985] 1H NMR (DMSOd6): 12.58 (1 H, br s), 11.80 (1 H, s), 7.86 (1 H, m), 4.50 (1 H, quin, J = 8.5 Hz), 4.18 (1 H, dd, J = 11.6, 9.2 Hz), 3.78 (1 H, dd, J = 11.7, 7.8 Hz), 3.41 (2 H, s), 3.30 (1 H, dd, J = 15.9, 9.3 Hz), 2.91 (1 H, dd, J = 15.8, 8.1 Hz ). 13

[00986] C NMR (DMSOd6): 170.7, 155.3, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144.6, 143, 7, 143.7, 143.7,

143.7, 143.6, 143.6, 129.4, 120.5, 120.3, 120.2, 113.4, 105.9, 105.7, 105.6, 48.5, 35, 7, 29.9, 29.1.

[00987] Example 16: (S) -2- (6- (5-bromo-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1,2- c] imidazol-1-yl) acetic

[00988] The compound was prepared analogously to Example 3 from 4- (5-bromo-2-fluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) pyrrolidine-1-carboxylate (4S) -tert -butyl and isolated as a yellow solid.

[00989] 1H NMR (DMSOd6): 12.58 (1 H, br s), 11.76 (1 H, br s), 7.59 (1 H, dd, J = 6.6, 2.5 Hz), 7.53 (1 H, ddd, J = 8.8, 4.5, 2.6 Hz), 7.23 (1 H, dd, J = 10.3, 8.8 Hz), 4 , 22 (1 H, quin, J = 7.9 Hz), 4.14 (1 H, dd, J = 11.2, 8.1 Hz), 3.74 (1 H, dd, J = 11, 2, 7.5 Hz), 3.43 (2 H, m), 3.21 (1 H, dd, J = 15.5, 8.1 Hz), 2.88 (1 H, dd, J = 15.4, 7.9 Hz). 13

[00990] C NMR (DMSOd6): 170.7, 160.3, 158.7, 155.5, 131.9, 131.8, 131.4, 131.4, 130.7, 130.6, 129.5, 118, 117.9, 116.5, 116.5, 113.7, 49.3, 40.4, 29.9, 29.4. Example 17: (R) -2- (6- (5-chloro-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole -1-il) acetic

[00991] The compound was prepared in an analogous manner to Example 3 from 4- (5-chloro-2-fluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) pyrrolidine-1-carboxylate (4R) -tert -butyl and isolated as a pale yellow solid.

[00992] 1H NMR (DMSOd6): 12.54 (1 H, m), 11.75 (1 H, s), 7.47 (1 H, dd, J = 6.5, 2.6 Hz) , 7.40 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.29 (1 H, dd, J = 9.9, 8.9 Hz), 4.22 (1 H, quin, J = 7.8 Hz), 4.14 (1 H, dd, J = 11.2, 8.0 Hz), 3.74 (1 H, dd, J = 11.3, 7.5 Hz), 3.42 (2 H, m), 3.22 (1 H, dd, J = 15.5, 8.1 Hz), 2.88 (1 H, dd, J = 15, 6, 7.8 Hz). 13

[00993] C NMR (DMSOd6): 170.7, 159.8, 158.2, 155.5, 130.3, 130.2, 129.5, 128.9, 128.9, 128.6, 128.5, 128.5, 128.5, 117.6, 117.4, 113.7, 49.3, 40.4, 29.9, 29.4.

[00994] Example 18: (R) -2- (6- (2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1,2-c] imidazol-1-yl) acetic

[00995] The compound was prepared analogously to Example 3 from 4- (2,6-difluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) pyrrolidine-1-carboxylate (4R) -tert-butyl and isolated as a pale pink solid.

[00996] 1H NMR (DMSOd6): 12.55 (1 H, br s), 11.76 (1 H, s), 7.41 (1 H, m), 7.13 (2 H, m) , 4.43 (1 H, quin, J = 8.8 Hz), 4.15 (1 H, dd, J = 10.6, 9.9 Hz), 3.72 (1 H, dd, J = 11.3, 8.4 Hz), 3.41 (2 H, m), 3.24 (1 H, dd, J = 15.7, 9.2 Hz), 2.86 (1 H, dd, J = 15.7, 8.7 Hz). 13

[00997] C NMR (DMSOd6): 170.7, 161.6, 161.6, 160, 159.9, 155.3, 129.8, 129.7, 129.7, 116.5, 116, 4, 113.3, 112.3, 112.2, 112.1, 112.1, 48.7, 35.3, 29.9, 29.3.

[00998] Example 19: (S) -N-cyano-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [1,2-c] imidazol-1-yl) acetamide

[00999] To a stirred suspension of (S) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [ 1,2-c] imidazol-1-yl) acetic (Example 10) (0.035 g, 0.1 mmol) in acetonitrile (1 mL) 1-hydroxypyrrolidine-2,5-dione (0.012 g, 0.100 mmol) was added followed by the addition of N, N'-methanediylidenodicyclohexanamine (0.021 g, 0.100 mmol). The reaction was stirred at room temperature for 1 h. The mixture was diluted with N, N-dimethylformamide (1 ml), to which cyanamide (4.20 mg, 0.100 mmol) was added followed by the addition of N-ethyl-N-isopropylpropan-2-amine (0.017 ml, 0.100 mmol) and the mixture was stirred for 16 h at room temperature. After that, insoluble materials were removed by filtration, the filtrate was diluted with saline, acidified and then extracted with dichloromethane. The organic phase was dried over MgSO4 and then concentrated under reduced pressure. The product was crystallized by grinding with petroleum ether as a beige powder. (Yield: 0.015 g, 40%.)

[001000] 1H NMR (DMSOd6): 11.94 (1 H, br), 11.79 (1 H, s), 7.86 (1 H, m), 4.50 (1 H, quin, J = 8.6 Hz), 4.19 (1 H, dd, J = 11.4, 9.4 Hz), 3.79 (1 H, dd, J = 11.7, 7.9 Hz), 3 , 56 (2 H, br s), 3.30 (1 H, br dd, J = 16.0, 9.2 Hz), 2.92 (1 H, dd, J = 16.0, 8.1 Hz). 13

[001001] C NMR (DMSOd6): 169.8, 155.8, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144, 6, 144.6, 143.8,

143.7, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 130.4, 120.3, 120.2, 120.1, 111, 7, 108.3, 105.9, 105.8, 105.6, 48.5, 35.8, 30.8, 29.1.

[001002] Example 20: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (methylsulfonyl) acetamide

[001003] To a stirred suspension of (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [ 1,2-c] imidazol-1-yl) acetic (Example 12) (100 mg, 0.257 mmol) in dry dichloromethane (3 mL) was added, in parts, di (1H-imidazol-1-yl) methanone (45 , 8 mg, 0.283 mmol) at room temperature to give a clear solution. The mixture was stirred for 30 min and then methanesulfonamide (26.9 mg, 0.283 mmol) was added followed by the addition of 2,3,4,6,7,8,9,10-octahydropyrimide [1,2 -a] azepine (0.039 ml, 0.257 mmol) and the mixture was stirred at room temperature for 16 h. The mixture was poured over 1 N HCl and extracted with ethyl acetate. The organic phase was washed with water and dried over MgSO4. The solvent was concentrated in vacuo and then purified by chromatography on a mixture of dichloromethane - methanol (9: 1). Recrystallization from a mixture of diethyl ether - isopropanol gave (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro- 2H-pyrrolo [1,2-c] imidazol-1-yl) - N- (methylsulfonyl) acetamide as a brown solid. Yield: 30 mg, 22%.

[001004] 1H NMR (DMSOd6): 11.67 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.17 (1 H, dt, J = 1.4, 9.4 Hz), 4.43 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 11.4, 9, 3 Hz), 3.72 (1 H, dd, J = 11.6, 8.1 Hz), 3.25 (2 H, s), 3.25 (1 H, dd, J = 9.5, 15.6 Hz), 2.95 (3 H, s), 2.86 (1

H, dd, J = 15.9, 8.4 Hz). 13

[001005] C NMR (DMSOd6): 171, 160.9, 160.8, 159.2, 159.2, 157.6, 157.5, 155.9, 155.9, 154.8, 132, 5, 132.4, 129.2, 118.8, 118.7, 118.5, 114.6, 113.8, 113.8, 113.7, 113.6, 104.1, 103.9, 48.5, 40.5, 35.7, 33.5, 29.5.

[001006] Example 21: (S) -2- (6- (5-bromo-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -N- (methylsulfonyl) acetamide

[001007] The compound was prepared analogously to Example 20 from (S) -2- (6- (5-bromo-2-fluorophenyl) -3-thioxo-2,5,6,7-tetra- hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a yellow solid.

[001008] 1H NMR (DMSOd6): 11.90 (1 H, br), 11.72 (1 H, s), 7.60 (1 H, dd, J = 6.6, 2.2 Hz) , 7.53 (1 H, ddd, J = 8.6, 4.4, 2.5 Hz), 7.23 (1 H, dd, J = 10.1, 9.0 Hz), 4.21 (1 H, quin, J = 7.9 Hz), 4.13 (1 H, dd, J = 11.1, 8.3 Hz), 3.73 (1 H, dd, J = 11.2, 7.7 Hz), 3.40 (2 H, m), 3.21 (1 H, br dd, J = 15.4, 8.1 Hz), 3.12 (3 H, s), 2, 88 (1 H, br dd, J = 15.4, 8.1 Hz). 13

[001009] C NMR (DMSOd6): 169.5, 160.3, 158.7, 155.4, 131.9, 131.8, 131.4, 131.4, 130.7, 130.6, 129.7, 118, 117.9, 116.5, 113.5, 49.2, 40.8, 40.4, 32.4, 29.6.

[001010] Example 22: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-oxotetrahydrofuran-3-yl) acetamide

[001011] A mixture of (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [1, 2-c] imidazol-1-yl) acetic (Example 13) (70 mg, 0.180 mmol), 3-aminodihydrofuran-2 (3H) -one hydrobromide (32.7 mg, 0.180 mmol), 3-hydrochloride - ((((ethylimino) methylene) amino) -N, N-dimethylpropan-1-amine (34.5 mg, 0.180 mmol), N, N-dimethylpyridin-4-amine (24.17 mg, 0.198 mmol), N -ethyl- N-isopropylpropan-2-amine (0.041 ml, 0.234 mmol) in dry N, N-dimethylformamide (3 ml) was stirred for 3 h at room temperature. After that, the solvent was removed under reduced pressure and the residue was diluted with ethyl acetate. The mixture was washed with aq. saturated NaHCO3 and saline, respectively. The organic phase was dried over MgSO4 and then evaporated. Chromatography on a mixture of dichloromethane and methanol (9: 1) gave the title product as a yellow solid. Yield: 50 mg, 53%.

[001012] 1H NMR (DMSOd6): 11.80 (1 H, s), 8.49 (1 H, dd, J = 7.8, 4.5 Hz), 7.73 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.17 (1 H, dt, J = 1.4, 9.6 Hz), 4.57 (1 H, dtd, J = 10, 6, 8.7, 8.7, 2.4 Hz), 4.44 (1 H, d quin, J = 8.7, 3.9 Hz), 4.34 (1 H, dt, J = 1 , 3, 9.0 Hz), 4.20 (1 H, ddd, J = 10.5, 8.7, 6.6 Hz), 4.15 (1 H, dd, J = 9.5, 11 , 3 Hz), 3.73 (1 H, dd, J = 11.5, 8.1 Hz), 3.31 (2 H, t, J = 5.9 Hz), 3.23 (1 H, td, J = 15.6, 9.4 Hz), 2.87 (1 H, ddd, J = 15.7, 10.7, 9.1 Hz), 2.39 (1 H, m), 2 , 15 (1 H, m). 13

[001013] C NMR (DMSOd6): 175.2, 167.8, 160.8, 160.8, 159.2, 159.2, 157.6, 157.5, 155.9, 155.9, 155.2, 132.5, 132.4, 129.5, 129.5, 118.7, 118.6, 118.6, 118.5, 118.4, 118.4, 113.8, 113, 8, 113.7, 113.6,

113.6, 113.6, 104.1, 104.1, 103.9, 103.9, 65.3, 48.6, 48.5, 48.1, 35.7, 35.7, 31, 2, 29.3, 28.2, 28.2.

[001014] Example 23: (R) -N- (methylsulfonyl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H -pyrrole [1,2-c] imidazol-1-yl) acetamide

[001015] Step 1: (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[001016] To a stirred suspension of (R) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [ 1,2-c] imidazol-1-yl) acetic (Example 15) (1.8 g, 5.20 mmol) in dry dichloromethane (35 ml) di (1H-imidazol-1-yl) was added in parts ) methanone (1.011 g, 6.24 mmol) at room temperature. The mixture was stirred for an additional 30 min, the resulting solid was collected, washed with petroleum ether and air-dried to give (R) -1- (1H-imidazol-1-yl) -2- (6- (2, 3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone as a beige powder. Yield: 1.70 g, 83%.

[001017] Step 2: (R) -N- (methylsulfonyl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazol-1-yl) acetamide

[001018] To a stirred suspension of methanesulfonamide (0.132 g, 1.388 mmol) and potassium tert-butoxide (0.142 g, 1.261 mmol) was added dry N, N-dimethylformamide (1, mL) at room temperature. After that, (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7- tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone (0.5 g, 1.261 mmol), and stirring was continued for 30 min. The reaction mixture was evaporated to dryness and the residue was partitioned between ethyl acetate (50 ml) and 1 M HCl (25 ml). The organic phase was dried over MgSO4 and then evaporated to dryness. The solid residue was slurried in ethyl acetate. The obtained solid was filtered, washed with ethyl acetate and diethyl ether, respectively, and then dried to ether, dried to give (R) -N- (methylsulfonyl) -2- (6- (2,3,5, 6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) acetamide as a light brown powder. Yield: 0.28 g, 52%.

[001019] 1H NMR (DMSOd6): 11.93 (1 H, br s), 11.83 (1 H, s), 7.86 (1 H, m), 4.50 (1 H, quin, J = 8.5 Hz), 4.19 (1 H, dd, J = 11.5, 9.3 Hz), 3.79 (1 H, dd, J = 11.6, 7.8 Hz), 3.49 (2 H, m), 3.29 (1 H, dd, J = 15.9, 9.3 Hz), 3.24 (3 H, m), 2.92 (1 H, dd, J = 8.2, 16.0 Hz). 13

[001020] C NMR (DMSOd6): 168.3, 155.6, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143, 7, 143.7, 143.7, 143.6, 143.6, 143.6, 130, 120.4, 120.3, 120.2, 112.2, 105.9, 105.7, 105, 6, 48.5, 41.1, 35.7, 31.5, 29.1.

[001021] Example 24: (R) -2- (6- (2,5-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole -1-yl) -N- (methylsulfonyl) acetamide

[001022] The compound was prepared in a manner analogous to Example 23 from (R) -2- (6- (2,5-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 14) and isolated as a yellow solid.

[001023] 1H NMR (DMSOd6): 11.93 (1 H, br s), 11.78 (1 H, s), 7.28 (2 H, m), 7.18 (1 H, m) , 4.23 (1 H, quin, J = 7.8 Hz), 4.14 (1 H, dd, J = 11.2, 8.0 Hz), 3.74 (1 H, dd, J = 11.2, 7.6 Hz), 3.50 (2 H, s), 3.25 (3 H, s), 3.22 (1 H, dd, J = 15.6, 8.1 Hz) , 2.87 (1 H, br dd, J = 15.6, 7.9 Hz). 13

[001024] C NMR (DMSOd6): 168.3, 159, 157.4, 157.1, 155.7, 155.5, 130.2, 130, 129.9, 129.9, 129.8, 117.1, 117.1, 117, 116.9, 115.5, 115.4, 115.3, 115.3, 115.3, 115.1, 115.1, 112.4, 49.3, 41.1, 40.2, 40, 31.5, 29.6.

[001025] Example 25: (R) - (2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] ethyl imidazol-1-yl) acetyl) glycinate

[001026] To a stirred mixture of ethyl ester hydrochloride of aminoacetic acid (0.070 g, 0.505 mmol) and triethylamine (0.07 mL, 0.550 mmol) in a mixture of dry tetrahydrofuran (2 mL) and N, N- dry dimethylformamide (0.2 ml) was added (R) -1- (1H-imidazole-

1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole- 1-yl) ethanone (Example 23, step 1) (0.1 g, 0.252 mmol). The reaction mixture was stirred for 30 min and then diluted with ethyl acetate. The organic phase was washed with sodium bicarbonate solution and 1 N HCl, respectively. After drying over MgSO4 the solvent was removed in vacuo. Crystallization from diethyl ether gave the title compound as a light beige powder. Yield: 0.053 g, 49%.

[001027] 1H NMR (DMSOd6): 11.77 (1 H, s), 8.38 (1 H, t, J = 5.9 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.6 Hz), 4.17 (1 H, dd, J = 11.5, 9.2 Hz), 4.07 (2 H, q, J = 7.0 Hz ), 3.82 (2 H, d, J = 5.9 Hz), 3.78 (1 H, dd, J = 11.6, 7.9 Hz), 3.32 (2 H, m), 3.26 (1 H, dd, J = 15.9, 9.3 Hz), 2.90 (1 H, dd, J = 15.8, 8.2 Hz), 1.16 (3 H, t , J = 7.1 Hz). 13

[001028] C NMR (DMSOd6): 169.7, 168.2, 155.3, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143, 7, 143.7, 143.7, 143.7, 143.6, 143.6, 129.2, 120.3, 120.2, 120.1, 113.9, 105.9, 105.7, 105.6, 60.4, 48.4, 40.9, 35.8, 31.1, 29.2, 14.

[001029] Example 26: (S) -2- (2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo- 2,5,6,7-tetrahydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) acetamido) propanamide

[001030] The compound was prepared in an analogous manner to Example 25 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone (Example 23 step 1) and isolated as a beige powder.

[001031] 1H NMR (DMSOd6): 11.75 (1 H, s), 8.14 (1 H, d, J = 7.5 Hz), 7.85 (1 H, m), 7.34 (1 H, br s), 7.02 (1 H, br s), 4.48 (1 H, quin, J = 8.6 Hz), 4.17 (2 H, m), 3.77 ( 1 H, dd, J = 11.6, 7.9 Hz), 3.30 (2 H, s), 3.26 (1 H, dd, J = 15.9, 9.3 Hz), 2, 88 (1 H, dd, J = 8.2, 15.9 Hz), 1.19 (3 H, d, J = 7.2 Hz). 13

[001032] C NMR (DMSOd6): 174.1, 167.3, 155.2, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.7, 144, 7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 129, 120.4, 120.3, 120.2, 114.4, 105.9, 105.7, 105.6, 48.4, 48.2, 35.8, 31.3, 29.2, 18.3.

[001033] Example 27: (R) -N- (cyanomethyl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazol-1-yl) acetamide

[001034] The compound was prepared analogously to Example 25 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone (Example 23 step 1) and isolated as a beige powder.

[001035] 1H NMR (DMSOd6): 11.82 (1 H, s), 8.66 (1 H, br t, J = 5.4 Hz), 7.86 (1 H, m), 4, 49 (1 H, quin, J = 8.6 Hz), 4.18 (1 H, dd, J = 11.4, 9.3 Hz), 4.14 (2 H, d, J = 5.6 Hz), 3.79 (1 H, dd, J = 11.6, 7.9 Hz), 3.35 (2H,

m), 3.26 (1 H, br dd, J = 15.8, 9.2 Hz), 2.90 (1 H, m). 13

[001036] C NMR (DMSOd6): 168.5, 155.5, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143, 6, 143.6, 143.6, 129.5, 120.3, 120.2, 120.1, 117.6, 113.4, 105.9, 105.7, 105.6, 48.4, 35.8, 30.9, 29.1, 27.2.

[001037] Example 28: N - ((1r, 4R) -4-hydroxycyclohexyl) -2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5 , 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

The compound was prepared analogously to Example 25 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone (Example 23 step 1) and isolated as a brown powder.

[001039] 1H NMR (DMSOd6): 11.74 (1 H, s), 7.85 (1 H, m), 7.82 (1 H, d, J = 7.7 Hz), 4.48 (1 H, quin, J = 8.4 Hz), 4.17 (1 H, dd, J = 9.4, 11.6 Hz), 3.77 (1 H, dd, J = 7.8, 11.6 Hz), 3.43 (1 H, m), 3.34 (1 H, m), 3.24 (1 H, br dd, J = 15.9, 9.3 Hz), 3, 20 (2 H, s), 2.87 (1 H, dd, J = 7.8, 15.8 Hz), 1.77 (2 H, m), 1.73 (2 H, br m), 1.16 (4 H, m). 13

[001040] C NMR (DMSOd6): 166.7, 155.1, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.7, 144.6, 143.7, 143, 7, 143.6, 143.6, 143.6, 143.6, 143.5, 143.5, 128.7, 120.5, 120.4, 120.3, 114.5, 105.8, 105.7, 105.5, 68.1, 48.4, 47.4, 35.7, 33.9, 31.5, 30.2, 29.3.

[001041] Example 29: N- (2-hydroxycyclohexyl) -2 - ((R) -6- (2,3,5,6-

tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[001042] The compound was prepared in an analogous manner to Example 25 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone (Example 23 step 1) and isolated as a brown powder.

[001043] 1H NMR (DMSOd6): 11.73 (1 H, m), 7.84 (2 H, m), 4.47 (1 H, m), 4.17 (1 H, m), 3.77 (1 H, m), 3.36 (1 H, m), 3.32-3.16 (4 H, m), 2.89 (1 H, m), 2.07-1, 0 (8 H, several multiplets). 13

[001044] C NMR (DMSOd6): 167.2, 167.2, 155.1, 146.4, 146.3, 146.2, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.8, 120.5, 120, 4, 120.3, 120.3, 120.2, 114.7, 105.9, 105.7, 105.5, 71.1, 54.5, 48.4, 35.7, 33.9, 31.8, 31.7, 30.9, 29.3, 29.2, 24.1, 23.8.

[001045] Example 30: (R) -N, N-dimethyl-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazol-1-yl) acetamide

[001046] The compound was prepared analogously to Example 25 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone (Example 23 step 1) and isolated as a khaki powder.

[001047] 1H NMR (DMSOd6): 11.70 (1 H, s), 7.84 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4.18 (1 H, dd, J = 11.6, 9.2 Hz), 3.77 (1 H, dd, J = 11.7, 7.8 Hz), 3.48 (2 H, s), 3 , 23 (1 H, dd, J = 15.8, 9.4 Hz), 2.98 (3 H, s), 2.86 (1 H, dd, J = 15.8, 8.1 Hz) , 2.82 (3 H, s). 13

[001048] C NMR (DMSOd6): 167.9, 155.1, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144, 7, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 129, 120.5, 120, 4, 120.3, 114.4, 105.9, 105.7, 105.6, 48.5, 37, 35.8, 35.1, 29.2, 29.1.

[001049] Example 31: (S) -2-amino-3- (2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7 -tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) acetamido) propanoic

[001050] To a solution of (S) -2 - ((tert-butoxycarbonyl) amino) -3- (2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo -3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) acetamido) propanoic (prepared analogously to Example 25 from (R) -1- ( 1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [1,2- c] imidazol-1-yl) ethanone (Example 23, step 1)) (0.3 g, 0.563 mmol) in tetrahydrofuran (4 ml) HCl cc was added. (1.17 mL, 14.08 mmol) at room temperature and the solution was stirred for 4 h. After that, the solvent was removed in vacuo, the residue was recovered in water

(about 10 mL) and then the resulting dark insoluble material was removed by filtration. The filtrate was neutralized to pH 7 by adding 5 M NaOH and then aged on ice for 30 min. The precipitate was collected, washed with a minimum volume of water and dried in vacuo at 50 ° C. The crude product was again slurried in acetone and then dried to give (S) -2-amino-3- (2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) acid -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) acetamido) propanoic as a beige powder. Yield: 0.11 g, 45%.

[001051] 1H NMR (DMSOd6): 10.4-6.5 (4H, br), 8.31 (1 H, br s), 7.84 (1 H, m), 4.48 (1 H , quin, J = 8.6 Hz), 4.17 (1 H, br dd, J = 11.1, 9.5 Hz), 3.77 (1 H, br dd, J = 11.7, 8 , 0 Hz), 3.54 (1H, m), 3.35 (1H, m), 3.32 (1H, m), 3.31 (2H, m), 3.29 (1H, m), 2.91 (1 H, br dd, J = 15.7, 8.2 Hz). 13

[001052] C NMR (DMSOd6): 168.8, 168.5, 155.2, 146.4, 146.4, 146.3, 146.3, 146.2, 146.2, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 143, 7, 143.7, 143.7, 143.7, 143.6, 143.6, 129.2, 120.3, 120.2, 120.1, 114.3, 105.9, 105.7, 105.6, 54.1, 48.4, 40.3, 35.8, 31.5, 29.1.

[001053] Example 32: ((R) -N-cyclopentyl-2- (6- (2,3,5,6-tetrafluorophenyl) - 3-thioxo-3,5,6,7-tetrahydro-2H- pyrrole [1,2-c] imidazol-1-yl) acetamide

[001054] To a stirred solution of aminocyclopentane (0.05 mL, 0.550 mmol) in dry tetrahydrofuran (2 mL) was added (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone (Example 23, step 1) (0.1 g,

0.252 mmol). The reaction was stirred 30 min at room temperature. After that, the mixture was diluted with ethyl acetate (about 10 ml), washed with a sodium bicarbonate solution, 1 M HCl, respectively. The organic phase was dried over MgSO4, filtered and evaporated to dryness. Crystallization from a mixture of diethyl ether - petroleum ether gave (R) -N-cyclopentyl-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6, 7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) acetamide as a beige powder. Yield: 0.064 g, 61%.

[001055] 1H NMR (DMSOd6): 11.74 (1 H, br s), 7.93 (1 H, br d, J = 7.0 Hz), 7.85 (1 H, m), 4 , 48 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.4, 9.3 Hz), 3.96 (1 H, sxt, J = 6, 8 Hz), 3.77 (1 H, dd, J = 11.7, 7.8 Hz), 3.25 (1 H, br dd, J = 15.8, 9.2 Hz), 3.21 (2 H, s), 2.87 (1 H, dd, J = 15.8, 7.9 Hz), 1.77 (2 H, m), 1.61 (2 H, m), 1, 48 (2 H, m), 1.35 (2 H, dq, J = 12.7, 6.6 Hz). 13

[001056] C NMR (DMSOd6): 166.9, 155.1, 146.4, 146.3, 146.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.6, 143.6, 143, 6, 143.6, 143.6, 128.8, 120.5, 120.4, 120.3, 114.6, 105.9, 105.7, 105.5, 50.5, 48.4, 35.7, 32.2, 32.2, 31.5, 29.3, 23.4.

[001057] Example 33: 2 - ((5aS, 6aR) -5a- (3,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetamide

[001058] Step 1: (1S, 5R) -4- (3 - ((tert-butoxycarbonyl) amino) -3-oxopropanoyl) -1- (3,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane -3- tert-butyl carboxylate

[001059] A solution of (1S, 5R) -1- (3,5-difluorophenyl) -4 - ((2,2-dimethyl-

4,6-dioxo-1,3-dioxan-5-ylidene) (hydroxy) methyl) -3-azabicyclo [3.1.0] tert-butyl hexane-3-carboxylate (1.0 g, 2.128 mmol) (Example 1, Step 10) and tert-butyl carbamate (0.252 g, 2.188 mmol) in acetonitrile (20 mL) was stirred at reflux for 3 h. The mixture was then evaporated to dryness and chromatographed twice (dichloromethane - methanol and then petroleum ether - ethyl acetate). The product was isolated as a light yellow oil. (Yield: 0.33 g, 27%).

[001060] Step 2: 3 - ((1R, 5S) -5- (3,5-difluorophenyl) -3-azabicyclo [3.1.0] hexan-2-yl) -3-oxopropanamide hydrochloride

[001061] A solution of (1S, 5R) -4- (3 - ((tert-butoxycarbonyl) amino) -3-oxopropanoyl) -1- (3,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane Tert-butyl carboxylate (0.33 g, 0.687 mmol) in 4 M HCl (1.37 mL, 5.49 mmol) in dioxane was stirred at room temperature for 4 h. The resulting precipitate was removed by filtration, washed with diethyl ether and dried in vacuo to give the product as a white solid. (Yield: 0.125 g, 52%).

[001062] Step 3: 2 - ((5aS, 6aR) -5a- (3,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetamide)

[001063] A hydrochloride solution of 3 - ((1R, 5S) -5- (3,5-difluorophenyl) - 3-azabicyclo [3.1.0] hexan-2-yl) -3-oxopropanamide (0.117 g, 0.369 mmol), potassium thiocyanate (0.0395 g, 0.406 mmol) and 6 M HCl (0.015 mL, 0.185 mmol) in a mixture of ethanol (1.5 mL) and water (1.5 mL) was stirred under reflux for 2 h. After that, the mixture was cooled to room temperature and the ethanol was evaporated. The residue was partitioned between water and dichloromethane and then an organic phase was dried over MgSO4, filtered and evaporated. Chromatography on a mixture of dichloromethane - methanol gave the title product as a light yellow solid. Yield: 0.031 g, 25%.

[001064] 1H NMR (DMSOd6): 11.63 (1 H, s), 7.36 (1 H, br s), 7.10 (3 H, m), 7.05 (1 H, br s ), 4.18 (1 H, d, J = 12.2 Hz), 4.03 (1 H, d, J = 12.2 Hz), 3.25 (2 H, m), 2.93 ( 1 H, dd, J = 8.4, 4.3 Hz), 1.67 (1 H, dd, J = 8.2, 5.3 Hz), 1.20 (1 H, t, J = 4 , 8 Hz). 13

[001065] C NMR (DMSOd6): 169.9, 163.4, 163.3, 161.8, 161.7, 156.1, 145, 144.9, 144.9, 131.9, 113, 7, 110, 110, 109.9, 109.8, 102.3, 102.1, 101.9, 50.8, 36.1, 31.2, 25.1, 23.

[001066] Example 34: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-oxocyclopentyl) acetamide

[001067] To a stirred suspension of (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [ 1,2-c] imidazol-1-yl) acetic (Example 12) (100 mg, 0.257 mmol) in dry tetrahydrofuran (2 mL) was added di (1H-imidazol-1-yl) methanone (50 mg, 0.308 mmol) and the mixture was stirred for 1 h. Thereafter, 2-aminocyclopentanone hydrochloride (77 mg, 0.565 mmol) and a reaction mixture was stirred for an additional 1 h. The mixture was then diluted with ethyl acetate (5 ml), washed with 1 M HCl solution. The organic phase was dried (MgSO4), filtered and desorbed to dryness in vacuo. The crude product was purified by chromatography on a mixture of dichloromethane - methanol (9: 1). The oil thus obtained was crystallized by trituration in n-heptane (light brown powder). Yield: 68 mg, 56%.

[001068] 1H NMR (DMSOd6): 11.78 (1 H, s), 8.18, 8.17 (1 H, 2 d, J = 3.4 Hz), 7.73 (1 H, m ), 7.17 (1 H, m), 4.43 (1 H, m), 4.15 (1 H, dd, J = 9.5, 11.3 Hz), 4.03 (1 H, m), 3.73 (1 H, dd, J = 11.5, 8.1 Hz), 3.28 (2 H, t, J = 5.1 Hz), 3.22 (1 H, m) , 2.86 (1 H, m), 2.24 (1 H, 2 m), 2.18-2.04 (2 H, m), 1.91 (1 H, m), 1.81 1.66 (2 H, m). 13

[001069] C NMR (DMSOd6): 214.8, 214.8, 167.5, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.3, 129.2, 118.7, 118.7, 118.6, 118.5, 118.5, 118.4, 113, 9, 113.9, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 56.3, 48.5, 35.7, 35, 6, 35.5, 31.2, 29.3, 28.7, 28.7, 17.9.

[001070] Example 35: (5aS, 6aR) -1- (2-aminoethyl) -5a- (3,5-difluorophenyl) -5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole hydrochloride [ 1,2-c] imidazole-3 (2H) -thione

[001071] To a stirred solution of 2 - ((5aS, 6aR) -5a- (3,5-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2- c] imidazol-1-yl) acetamide (Example 33) (52 mg, 0.162 mmol) in dry tetrahydrofuran (1 mL), sodium borohydride (0.032 g, 0.809 mmol) was added ) at room temperature, and then the mixture was cooled to 0 ° C. A solution of boron trifluoride diethyl etherate (0.103 mL, 0.809 mmol) in dry tetrahydrofuran (0.5 mL) was added dropwise to the above mixture, where the reaction was allowed to warm to room temperature and stirred for 2 h. After that, the reaction was cooled down again to 0 ° C and mitigated with 1 M HCl (~ 0.3 ml), followed by addition of 2 M HCl (~ 0.2 ml, for pH = 1). The mixture was then allowed to warm to room temperature and heated to reflux for 30 min. After that, the mixture was cooled to room temperature, diluted with water, and then the tetrahydrofuran was removed by evaporation. The aqueous phase was extracted with dichloromethane, where the organic phase was dried over MgSO4, filtered and evaporated to dryness to give the product as a yellow solid. Yield: 0.037 g, 60%).

[001072] 1H NMR (DMSOd6): 11.78 (1 H, s), 7.77 (3 H, br s), 7.13 (1 H, tt, J = 2.3, 9.3 Hz ), 7.11 (2 H, m), 4.19 (1 H, d, J = 12.2 Hz), 4.00 (1 H, d, J = 12.2 Hz), 3.05 ( 2 H, m), 2.97 (1 H, dd, J = 8.2, 4.4 Hz), 2.71 (2 H, m), 1.69 (1 H, dd, J = 8, 3, 5.2 Hz), 1.24 (1 H, t, J = 4.8 Hz). 13

[001073] C NMR (DMSOd6): 163.4, 163.3, 161.8, 161.7, 156.8, 144.9, 144.8, 144.8, 132.1, 114.1, 110.2, 110.1, 110, 110, 102.4, 102.2,

102, 50.8, 37.5, 36.3, 24.9, 22.5, 22.4.

[001074] Example 36: 2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetonitrile

[001075] Step 1: 4- (2-cyanoacetyl) -1- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] (1S, 5R) -tert-butyl hexane-3-carboxylate

[001076] To a cooled mixture (-78 ° C) of acetonitrile (0.357 ml, 6.79 mmol) and dry tetrahydrofuran (10 ml) was added 1.6 N n-butyl lithium (6.19 ml, 9.90 mmol) drop by drop. The mixture was stirred in the cold for 30 min and then a solution of 2-methyl 5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-2,3- was added dropwise (1R, 5S) -3-tert-butyl dicarboxylate (2 g, 5.66 mmol) (Example 4, step 1) in anhydrous tetrahydrofuran (5 ml). The reaction mixture was stirred in the cold for 3 h and then mitigated by adding 1 M HCl (9.90 mL, 9.90 mmol. After that, the mixture was allowed to warm to room temperature and the pH of the mixture it was adjusted to 3 by adding 1M HCl. The mixture was then partitioned between diethyl ether and saline, the organic phase was separated, dried over MgSO4, filtered and evaporated to dryness. The resulting yellow oil was purified by chromatography (ether oil - ethyl acetate; 9: 1, 4: 1, then 2: 1) (Yield: 1.31 g, 57%).

[001077] Step 2: 3 - ((1R, 5S) -5- (2,5-difluorophenyl) -3- azabicyclo [3.1.0] hexan-2-yl) -3-oxopropanonitrile hydrochloride

[001078] A mixture of 4- (2-cyanoacetyl) -1- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate of (1S, 5R) -tert-butyl (1, 3 g, 3.59 mmol) and a solution of 4 M HCl in dioxane (17.94 mL, 71.7 mmol) was stirred at room temperature for 4 h. Diethyl ether was then added and the mixture was stirred for 15 min. The resulting yellow solid was removed by filtration and dried in vacuo. (Yield: 0.96 g, 81%).

[001079] Step 3: 2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetonitrile

[001080] To a hydrochloride solution of 3 - ((1R, 5S) -5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexan-2-yl) -3-oxopropanonitrile (950 mg, 3.18 mmol) in a mixture of ethanol (13 mL) and water (13 mL) was added potassium thiocyanate (340 mg, 3.50 mmol) followed by addition of cc HCl (0.131 mL, 1.590 mmol). The solution was heated to reflux for 1 h and then cooled to room temperature. After that, the ethanol was removed by evaporation, and the aqueous phase was extracted with dichloromethane. The organic phase was separated and evaporated to dryness. Chromatography (dichloromethane - methanol (98: 2, then 95: 5) gave the product as a yellow foam. (Yield: 0.35 g, 32%).

[001081] 1H NMR (DMSOd6): 12.06 (1 H, s), 7.29 (2 H, m), 7.22 (1 H, m), 4.10 (1 H, d, J = 12.0 Hz), 3.91 (2 H, m), 3.82 (1 H, d, J = 12.0 Hz), 2.90 (1 H, dd, J = 8.4, 4 , 3 Hz), 1.72 (1 H, dd, J = 8.4, 5.5 Hz), 1.23 (1 H, t, J = 4.8 Hz). 13

[001082] C NMR (DMSOd6): 158.8, 158.6, 157.4, 157.2, 157, 132.5, 128.3, 128.3, 128.2, 128.2, 117, 2, 117.1, 117.1, 117, 117, 117, 116.1, 116, 115.9, 115.9, 108.8, 51.6, 51.6, 32.7, 21.9, 20.5, 13.4.

[001083] Example 37: N-benzyl-2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N-methylacetamide

[001084] Step 1: 1- (2,5-difluorophenyl) -4- (3-ethoxy-3-oxopropanoyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (1S, 5R) -tert- butyl

[001085] To a stirred mixture of ethyl and potassium malonate (3.39 g, 19.89 mmol) in dry tetrahydrofuran (43 mL) was added magnesium bromide diethyl etherate (3.42 g, 13.26 mmol), at room temperature under an inert atmosphere, and then the white suspension thus obtained was heated to 50 ° C for 3 h (1st mixture).

[001086] In parallel, 1,1'-carbonyldiimidazole (3.66 g, 22.54 mmol) was added, in parts, to a light yellow solution of acid (1R, 5S) - 3- (tert-butoxycarbonyl) -5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-2-carboxylic (Example 4, step 1) (4.5 g, 13.26 mmol) in dry tetrahydrofuran (35 mL ) at 0 ° C, under nitrogen. The yellow solution thus obtained was allowed to warm to room temperature, stirred for 2 h and then added to the first suspension at room temperature, drop by drop. After that, the reaction was stirred at room temperature for 24 h, and the mixture was quenched with sodium hydrogensulfate. The aqueous phase was extracted with a mixture of ethyl acetate - petroleum ether (2: 1). The combined organic phases were washed with saturated sodium bicarbonate solution, dried over MgSO4, filtered and evaporated to dryness. Chromatography (ethyl acetate - petroleum ether; 9: 1, then 4: 1) gave the product as a clear oil. (Yield: 3.52 g, 61%).

[001087] Step 2: 4- (3- (benzyl (methyl) amino) -3-oxopropanoyl) -1- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (1S , 5R) -tert-butyl

[001088] To a stirred solution of 1- (2,5-difluorophenyl) -4- (3-ethoxy-3-oxopropanoyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (1S, 5R) - tert-butyl (1 g, 2.422 mmol) in toluene (4 mL) N-methylbenzylamine (0.63 mL, 4.88 mmol) was added followed by the addition of N, N-dimethylpyridin-4-amine (0.090 g, 0.733 mmol) at room temperature. The solution was heated to 100 ° C for 20 h, then cooled to room temperature, diluted with a mixture of ethyl acetate - petroleum ether (1: 1) and washed with 1 M HCl. The organic phase was dried over MgSO4, filtered and evaporated to dryness. The yellow oil thus obtained was purified by chromatography (petroleum ether - ethyl acetate; 4: 1, then 2: 1) to leave the product as an oil yellow. (Yield: 0.88 g, 67%).

[001089] Step 3: N-benzyl-3 - (((1R, 5S) -5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexan-2-yl) -N-methyl- hydrochloride 3-oxopropanamide

[001090] A mixture of 4- (3- (benzyl (methyl) amino) -3-oxopropanoyl) -1- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (1S , 5R) - tert-butyl (870 mg, 1.796 mmol) and 4 M HCl in dioxane (6.7 mL, 26.9 mmol) was stirred at room temperature for 2 h. Diethyl ether was then added and the suspension was stirred for 15 min. The resulting off-white precipitate was filtered and dried in vacuo. (Yield: 0.57 g, 67%).

[001091] Step 4: N-benzyl-2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) -N-methylacetamide

[001092] To a stirred solution of N-benzyl-3 - ((1R, 5S) - 5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexan-2-yl) -N- methyl-3-oxopropanamide (556 mg, 1.321 mmol) in a mixture of ethanol (5.4 mL) and water (5.4 mL) was added potassium thiocyanate (0.141 mg, 1.453 mmol) followed by addition of cc HCl. (0.054 mL, 0.661 mmol). The solution was heated to reflux for 1 h and then cooled to room temperature. After that, the ethanol was removed by evaporation and the aqueous phase was extracted with dichloromethane. The organic phase was then dried over MgSO4, filtered and evaporated to dryness to give the product as a light yellow semi-solid. (Yield: 0.17 g, 29%).

[001093] 1H NMR (DMSOd6): 11.70 (0.65 H, s), 1.68 (0.35 H, s), 7.38 (0.7 H, t, J = 7.8 Hz), 7.34-7.17 (7.3 H, m), 4.64 (0.7 H, s), 4.53 (1.3 H, m), 4.09, 4.08 (1 H, 2 d, J = 12Hz), 3.81, 3.79 (1 H, 2 d, J = 12Hz), 3.69-3.58 (2 H, m), 2.98 (1 , 95 H, s), 2.81 (1.05 H, s), 2.76 (0.35 H, dd, J = 8.4, 4.3 Hz), 2.72 (0.65 H , dd, J = 8.3, 4.2 Hz), 1.63 (1 H, m), 1.11 (0.65 H, t, J = 4.8 Hz), 1.09 (0, 35 H, t, J = 4.8 Hz). 13

[001094] C NMR (DMSOd6): 168.3, 158.8, 158.6, 157.2, 157, 155.9, 137.5, 137.1, 131.8, 131.7, 128, 7, 128.7, 128.6, 128.5, 128.5, 128.4, 127.7, 127.3, 127.1, 126.8, 117.2, 117.1, 117, 117, 117, 116.9, 116.8, 116.8, 116.8, 115.9, 115.9, 115.8, 115.7, 113.9, 52.6, 51.5, 50.2, 35, 33.

[001095] Example 38: N-butyl-2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N-methylacetamide

[001096] The compound was prepared analogously to Example 37 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane -2-carboxylic and isolated as a light yellow foam.

[001097] 1H NMR (DMSOd6): 11.62 (1 H, 2 s), 7.29 (1 H, td, J = 9.4, 4.6 Hz), 7.25 (1 H, ddd , J = 9.1, 5.9, 3.2 Hz), 7.20 (1 H, m), 4.08 (1 H, d, J = 11.9 Hz), 3.81 (1 H , d, J = 12.2 Hz), 3.53 (2 H, m), 3.29 (2 H, m), 2.99

(1.65 H, s), 2.82 (1.35 H, s), 2.79, 2.78 (1 H, 2 dd, J = 8.3, 4.1 Hz), 1.65 (1 H, dd, J = 8.4, 5.3 Hz), 1.52 (0.9 H, m), 1.43 (1.1 H, m), 1.30 (0.9 H , m), 1.24 (1.1 H, m), 1.11 (1 H, m), 0.92 (1.35 H, t, J = 7.4 Hz), 0.87 (1 , 65 H, t, J = 7.3 Hz). 13

[001098] C NMR (DMSOd6): 167.7, 167.6, 158.8, 158.6, 157.2, 157, 155.8, 131.7, 131.6, 128.7, 128, 6, 128.6, 128.5, 117.2, 117.1, 117, 117, 116.8, 115.9, 115.9, 115.8, 115.7, 114.1, 114, 51, 5, 49.1, 46.8, 35.1, 33.2, 32.4, 30, 29.5, 28.9, 28.9, 22.3, 22.2, 20.9, 20, 8, 19.5, 19.4,

1.

[001099] Example 39: (5aS, 6aR) -1- (2- (butyl (methyl) amino) ethyl) -5a- (2,5-difluorophenyl) -5,5a, 6,6a-tetrahydrocyclopropa hydrochloride [3.4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001100] The compound was prepared analogously to Example 35 from N-butyl-2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo- 2,3,5,5a , 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N-methylacetamide (Example 37) and isolated as a light yellow solid.

[001101] 1H NMR (DMSOd6): 11.81 (1 H, br s), 9.25 (1 H, br s), 7.30 (1 H, m), 7.27 (1 H, m ), 7.22 (1 H, m), 4.08 (1 H, br d, J = 12.2 Hz), 3.81 (1 H, d, J = 12.0 Hz), 3.17 (2 H, br m), 2.95 (2 H, m), 2.93 (1 H, dd, J = 8.2, 4.2 Hz), 2.81 (2 H, br m), 2.69 (3 H, br s), 1.67 (1 H, br dd, J = 8.2, 5.3 Hz), 1.57 (2 H, br m), 1.31 (2 H , dq, J = 14.9, 7.4 Hz), 1.18 (1 H, br t, J = 4.7 Hz), 0.91 (3 H, t, J = 7.3 Hz).

[001102] C NMR (DMSOd6): 158.8, 158.7, 157.2, 157.1, 156.5, 131.6, 128.6, 128.5, 128.5, 128.4, 117.2, 117.2, 117.1, 117, 117, 116.8, 116, 116, 115.9, 115.8, 55.1, 53.5, 51.5, 39.8, 32, 6, 26, 22.2, 20.5, 19.8, 19.5, 13.6.

[001103] Example 40: (5aS, 6aR) -1- (2- (benzyl (methyl) amino) ethyl) -5a- (2,5-difluorophenyl) -5,5a, 6,6a-tetrahydrocyclopropa [3 , 4] pyrrole [1,2- c] imidazole-3 (2H) -thione

[001104] The compound was prepared in an analogous way to Example 35 from N-benzyl-2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo- 2,3,5,5a , 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N-methylacetamide (Example 37) and isolated as a white foam.

[001105] 1H NMR (CDCl3): 10.33 (1 H, br s), 7.37 (2 H, t, J = 7.3 Hz), 7.33 (2 H, t, J = 8 , 5 Hz), 7.29 (1 H, t, J = 7.3 Hz), 7.05 (1 H, td, J = 9.1, 4.5 Hz), 7.00-6.93 (2 H, m), 4.25 (1 H, d, J = 12.2 Hz), 4.03 (1 H, d, J = 12.3 Hz), 3.57 (2 H, m) , 2.67 (4 H, m), 2.51 (1 H, dd, J = 8.2, 4.1 Hz), 2.28 (3 H, s), 1.58 (1 H, dd , J = 8.2, 5.5 Hz), 1.12 (1 H, m). 13

[001106] C NMR (CDCl3): 159.3, 158.9, 157.6, 157.2, 155.8, 137.5, 130.3, 129.4, 128.6, 128.1, 128.1, 128, 128, 127.5, 119.3, 117.1, 117, 116.9, 116.8, 116.7, 116.7, 116.5, 116.5, 116, 115, 9, 115.8, 115.8, 62.8, 55.8, 52.1, 52.1, 41.5, 32.7, 22.3, 21.2, 20.9.

[001107] Example 41: (5aS, 6aR) -1 - ((1H-tetrazol-5-yl) methyl) -5a- (2,5-difluorophenyl) -5.5a, 6.6a-tetrahydrocyclopropa [3 , 4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001108] To a stirred solution of 2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2- c] imidazol-1-yl) acetonitrile (Example 36) (50 mg, 0.165 mmol) in dry toluene (1 mL) was added dibutyltin oxide (41.0 mg, 0.165 mmol) followed by addition of azidotrimethylsilane (0.044 mL, 0.330 mmol). The reaction mixture was heated to 100 ° C for 24 h. The mixture was then cooled to room temperature, partitioned between diethyl ether and 1 M sodium hydroxide (1.6 ml) and the aqueous phase was washed with diethyl ether. The ethereal phase was discarded and the aqueous phase was acidified with 2 M HCl to pH = 1. The resulting solid was collected by filtration, washed with water and dried under vacuum. (Yield: 25 mg, 37%).

[001109] 1H NMR (DMSOd6): 11.85 (1 H, s), 7.29 (1 H, td, J = 9.4, 4.5 Hz), 7.25 (1 H, ddd, J = 9.0, 5.9, 3.2 Hz), 7.21 (1 H, m), 4.18 (2 H, m), 4.10 (1 H, br d, J = 12, 0 Hz), 3.80 (1 H, br d, J = 5.7 Hz), 2.69 (1 H, dd, J = 8.3, 4.2 Hz), 1.63 (1 H, dd, J = 8.4, 5.3 Hz), 1.20 (1 H, t, J = 4.8 Hz). 13

[001110] C NMR (DMSOd6): 158.8, 158.6, 157.2, 157, 156.8, 153.1, 132.4, 128.5, 117.2, 116.9, 115, 9, 51.6, 32.6, 22, 20.5, 19.3.

[001111] Example 42: (5aS, 6aR) -5a- (2,5-difluorophenyl) -1- (2-hydroxyethyl) -5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1, 2-c] imidazole-3 (2H) -thione

[001112] The compound was prepared analogously to Example 8 from 2 - ((5aS, 6aR) -5a- (2,5-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a -hexa- hydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) ethyl acetate and isolated as a yellow solid.

[001113] 1H NMR (DMSOd6): 11.65 (1 H, br s), 7.28 (2 H, m), 7.20 (1 H, m), 4.75 (1 H, t, J = 5.3 Hz), 4.06 (1 H, br d, J = 12.0 Hz), 3.79 (1 H, d, J = 12 Hz), 3.60 (2 H, m), 2.88 (1 H, dd, J = 8.2, 4.1 Hz), 2.55 (2 H, m), 1.61 (1 H, dd, J = 8.1, 5 , 4 Hz), 1.14 (1 H, t, J = 4.7 Hz). 13

[001114] C NMR (DMSOd6): 158.8, 158.6, 157.2, 157, 155.7, 130.9, 128.9, 128.8, 128.7, 128.7, 117, 2, 117.1, 117, 117, 116.9, 116.9, 116.8, 116.7, 116.7, 115.9, 115.8, 115.7, 115.6, 59.4, 51.4, 51.4, 32.4, 28, 22.5, 20.6.

[001115] Example 43: (S) -6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole-1 -carboxylic

[001116] Step 1: 4- (3,5-difluorophenyl) -2- (hydroxymethyl) pyrrolidine-1-(4S) -tert-butyl carboxylate

[001117] To a stirred solution of (4S) -1- (tert-butoxycarbonyl) - 4- (3,5-difluorophenyl) pyrrolidine-2-carboxylic acid (Example 44, step 9) (1.4 g, 4, 28 mmol) in isopropyl acetate (7 mL) was added sodium borohydride (0.259 g, 6.84 mmol) at 0-5 ° C followed by addition of boron trifluoride etarate (1.084 mL, 8.55 mmol The mixture was stirred for 2 h in the cold, then mitigated with 0.5 M sodium hydroxide (30.8 ml, 15.4 mmol), and allowed to stir at room temperature for 30 min. dried over MgSO4,

evaporated to dryness to leave a yellowish oil. Yield: 1.37 g, 97%).

[001118] Step 2: (4S) -tert-butyl 4- (3,5-difluorophenyl) -2-formylpyrrolidine-1-carboxylate

[001119] To a stirred solution of 4- (3,5-difluorophenyl) -2- (hydroxymethyl) pyrrolidine-1-carboxylate (4S) -tert-butyl (0.46 g, 1.468 mmol) in dry dichloromethane (14 mL) Dess-Martin periodinane (3-oxo-1λ5-benzo [d] [1,2] iodaoxol-1,1,1 (3H) -triyl) triacetate (0.623 g, 1.468 mmol) was added in one part to give a clear solution. Thereafter, the mixture was stirred at room temperature for 3 h, concentrated to approximately one third and subjected to chromatography (petroleum ether - ethyl acetate 9: 1, then 4: 1). The product was isolated as a yellowish oil. (Yield: 1.21 g, 94%).

[001120] Step 3: 2- (cyan (hydroxy) methyl) -4- (3,5-difluorophenyl) pyrrolidine-1-carboxylate (4S) -tert-butyl

[001121] To a stirred solution of 4- (3,5-difluorophenyl) -2-formylpyrrolidine-1-carboxylate (4S) -tert-butyl (1.2 g, 3.85 mmol) in a mixture of tetra- hydrofuran (10 ml) and water (5 ml) potassium cyanide (0.301 g, 4.63 mmol) was added followed by the addition of cc HCl (0.319 ml, 3.85 mmol). The mixture was stirred for 8 h, then extracted with dichloromethane. The organic phase was washed with brine, dried over MgSO4 and evaporated to dryness to give 2- (cyan (hydroxy) methyl) -4- (3,5-difluorophenyl) pyrrolidine-1-carboxylate (4S) -tert- butyl as a yellow oil. (Yield: 1.44 g, 99%).

[001122] Step 4: 4- (3,5-difluorophenyl) -2- (4S) -tert-butyl (2-ethoxy-1-hydroxy-2-oxoethyl) pyrrolidine-1-carboxylate

[001123] A mixture of 2- (cyano (hydroxy) methyl) -4- (3,5-difluorophenyl) pyrrolidine-1-carboxylate (4S) -tert-butyl (1.43 g, 3.80 mmol) and 2M HCl (28.5 ml, 57.1 mmol) was stirred at reflux for 16 h. After cooling to room temperature the mixture was filtered through a pad of celite to remove colored product, and then the filtrate was evaporated to dryness in vacuo. The residue was azeotroped twice with dry ethanol and the residue was recovered in abs ethanol. (20 mL). The solution thus obtained was treated with 4 M HCl (9.51 ml, 38.0 mmol) in dioxane and stirred under reflux for 2 h. The mixture was evaporated to dryness and then azeotroped with abs ethanol. The resulting semisolid was recovered in abs ethanol. (30 mL), neutralized by adding triethylamine to pH = 6-7, then a second crop of triethylamine (0.530 mL, 3.80 mmol) was added, followed by addition of di-tert-butyl dicarbonate (0.830 g, 3.80 mmol). The reaction was allowed to stir at room temperature for 2 h, and then evaporated to dryness at 40 ° C. The residue was partitioned between dichloromethane and water, the organic phase was dried over MgSO4 and concentrated under reduced pressure. Chromatography (petroleum ether - ethyl acetate; 9: 1, then 4: 1) gave the product as a yellow oil. (Yield: 1.16 g, 79%).

[001124] Step 5: (4S) -tert-butyl 4- (3,5-difluorophenyl) -2- (2-ethoxy-2-oxoacetyl) pyrrolidine-1-carboxylate

[001125] To a stirred solution of 4- (3,5-difluorophenyl) -2- (2-ethoxy-1-hydroxy-2-oxoethyl) pyrrolidine-1-carboxylate of (4S) -tert-butyl (1.15 g, 2.98 mmol) in dry dichloromethane (25 mL) Dess-Martin periodinane (3-oxo-1λ5-benzo triacetate [d] [1,2] iodaoxole-1,1,1 (3H) - triyl) (1.266 g, 2.98 mmol) at room temperature in one part and the mixture was stirred for 2 h. The reaction mixture was concentrated in vacuo, after which the residue was purified by chromatography (petroleum ether - ethyl acetate; 4: 1). The product was isolated as a yellowish oil. (1.08 g, 94% yield).

[001126] Step 6: 2 - ((4S) -4- (3,5-difluorophenyl) pyrrolidin-2-yl) -2-oxoacetate ethyl hydrochloride

[001127] To a stirred solution of 4- (3,5-difluorophenyl) -2- (2-ethoxy-2-oxoacetyl) pyrrolidine-1-carboxylate (4S) -tert-butyl (0.4 g, 1.043 mmol ) in 4 M HCl (5.22 mL, 20.87 mmol) in dioxane was stirred at room temperature for 4 h. The reaction mixture was diluted with a mixture of diethyl ether (20 ml) and petroleum ether (5 ml) and stirred for 30 min. After that, the resulting precipitate was collected, washed with diethyl ether, petroleum ether and dried under vacuum at 50 ° C to give 2 - ((4S) -4- (3,5-difluorophenyl) pyrrolidin-2-yl hydrochloride ) Ethyl -2-oxoacetate as a white powder. (Yield: 0.34 g, 92%).

[001128] Step 7: 6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole-1-carboxylate (S ) -ethyl

[001129] A solution of ethyl 2 - ((4S) -4- (3,5-difluorophenyl) pyrrolidin-2-yl) -2-oxoacetate (0.33 g, 1.032 mmol), 6 M HCl ( 0.086 mL, 0.516 mmol) and potassium thiocyanate (0.110 g, 1.135 mmol) in a mixture of ethanol (5 mL) and water (5 mL) was stirred under reflux for 30 min. The reaction was then cooled to room temperature, and the resulting solid was collected, washed with a mixture of ethanol and water (1: 1), and dried under vacuum at 50 ° C to give 6- (3,5-difluorophenyl) (S) -ethyl-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole-1-carboxylate as a white solid. (Yield: 0.28 g, 84%).

[001130] Step 8: (S) -6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole-1 -carboxylic

[001131] To a stirred solution of 6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole-1-carboxylate (S) -ethyl (0.08 g, 0.247 mmol) in methanol (2 mL) 5 M sodium hydroxide (0.148 mL, 0.740 mmol) was added at room temperature and the solution was stirred for 24 h. The mixture was then diluted with water (2 ml) and a second crop of 5 M sodium hydroxide (0.148 ml, 0.740 mmol) was added and the mixture was stirred for 48 h. The methanol was removed under vacuum, the residue was diluted with water (about 5 ml) and then acidified to pH = 2 by adding 6M HCl. The precipitate was collected, washed with water and dried under vacuum at 50 ° C to give (S) -6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole-1-carboxylic acid as white powder .

[001132] (Yield: 0.052 g, 71%).

[001133] 1H NMR (DMSOd6): 12.95 (1 H, br s), 12.49 (1 H, s), 7.16 (3 H, m), 4.28 (1 H, dd, J = 11.1, 8.3 Hz), 4.20 (1 H, quin, J = 8.6 Hz), 3.76 (1 H, dd, J = 11.0, 8.8 Hz), 3.47 (1 H, dd, J = 16.7, 8.1 Hz), 3.10 (1 H, dd, J = 16.7, 9.3 Hz). 13

[001134] C NMR (DMSOd6): 163.3, 163.2, 161.7, 161.6, 159.5, 158.9, 145, 145, 144.9, 140.4, 112.6, 110.9, 110.9, 110.8, 110.8, 102.8, 102.6, 102.4, 50.8, 45.7, 32.3.

[001135] Example 44: 2- (5a- (thiophen-2-yl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c ] imidazol-1-yl) ethyl acetate

[001136] The compound was prepared analogously to Example 4 from 3- (tert-butoxycarbonyl) -5- (thiophen-2-yl) -3-azabicyclo [3.1.0] hexane-2-carboxylic acid and isolated like orange foam.

[001137] 1H NMR (DMSOd6): 11.74 (1 H, s), 7.44 (1 H, dd, J = 5.1, 1.3 Hz), 7.11 (1 H, dd, J = 3.6, 1.2 Hz), 7.00 (1 H, dd, J = 5.1, 3.6 Hz), 4.16 (1 H, d, J = 12.0 Hz), 4.10 (2 H, q, J = 7.2 Hz), 4.00 (1 H, d, J = 12.0 Hz), 3.55 (2 H, m), 2.68 (1 H , dd, J = 8.4, 4.0 Hz), 1.83 (1 H, dd, J = 8.4, 5.6 Hz), 1.24 (1 H, dd, J = 5.4 , 4.5 Hz), 1.20 (3 H, t, J = 7.1 Hz). 13

[001138] C NMR (DMSOd6): 169.2, 156.4, 143.6, 132.2, 127.5, 125.1, 124.7, 112.3, 60.7, 52.2, 32.7, 29.7, 24.9, 24.3, 14.1.

[001139] Example 45: (S) -6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole-1- carbaldehyde

[001140] Step 1: 4- (3,5-difluorophenyl) -2- (4S) -tert-butyl (2- (methylsulfinyl) acetyl) pyrrolidine-1-carboxylate

[001141] To a solution of dimethyl sulfoxide (0.543 mL, 7.64 mmol) in dry tetrahydrofuran (5 mL) was added 1.6 M methyl lithium (4.77 mL, 7.64 mmol) in diethyl ether with cooling with external cold water bath. The mixture was allowed to warm to room temperature and stirred for 40 min. After that, a solution of (4S) -1- (tert-butoxycarbonyl) -4- (3,5-difluorophenyl) pyrrolidine-2-carboxylic acid was added dropwise (Example 1, step 9) (0, 5 g, 1.528 mmol) and di (1H-imidazol-1-yl) methanone (0.248 g, 1.528 mmol) in dry tetrahydrofuran (5 mL) with cooling with an external ice-water bath and the mixture was allowed to warm to at room temperature and stirring under nitrogen for 30 min. The mixture was then cooled to 0 ° C and neutralized by adding 2 M HCl (3.82 ml, 7.64 mmol) to pH = 4-5, followed by addition of saline. The mixture was extracted with a mixture of ethyl acetate - petroleum ether (2: 1) and the organic phase was dried over MgSO4 and evaporated to dryness to give the product as a yellowish oil. (Yield: 0.44 g, 74%).

[001142] Step 2: 1 - ((4S) -4- (3,5-difluorophenyl) pyrrolidin-2-yl) -2- (methylsulfinyl) ethanone hydrochloride

[001143] A stirred mixture of 4- (3,5-difluorophenyl) -2- (2- (methylsulfinyl) acetyl) pyrrolidine-1-carboxylate (4S) -tert-butyl (0.43 g, 1.110 mmol) and 4 M HCl (5.55 mL, 22.20 mmol) in dioxane was stirred at room temperature for 2 h. The mixture was then diluted with a mixture of diethyl ether - petroleum ether, aged for 30 min, the liquid supernatant was decanted from the separated oil, which solidified on standing under a high vacuum to give 1 - ((4S) - 4 hydrochloride - (3,5-difluorophenyl) pyrrolidin-2-yl) -2- (methylsulfinyl) ethanone. (Yield: 0.32 g, 89%).

[001144] Step 3: (S) -6- (3,5-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-

2H-pyrrolo [1,2-c] imidazole-1-carbaldehyde

[001145] A hydrochloride solution of 1 - ((4S) -4- (3,5-difluorophenyl) pyrrolidin-2-yl) -2- (methylsulfinyl) ethanone (0.31 g, 0.957 mmol), 6 M HCl (0.080 ml, 0.479 mmol) and potassium thiocyanate (0.099 g, 1.019 mmol) in a mixture of ethanol (4 ml) and water (4 ml) was stirred under reflux for 30 min. After that, the reaction was cooled to room temperature, diluted with water, the resulting solid was removed by filtration and the mother liquor was extracted with dichloromethane. The organic phase was dried over MgSO4, and evaporated to dryness. The residue was combined with the first precipitate and then recrystallized from ethyl acetate to give (S) -6- (3,5-difluorophenyl) -3-thioxo 3,5,6,7-tetrahydro-2H -pyrrole [1,2-c] imidazole-1-carbaldehyde as a beige powder. (Yield: 0.035 g, 13%).

[001146] 1H NMR (DMSOd6): 12.76 (1 H, br s), 9.36 (1 H, s), 7.18 (3 H, m), 4.31 (1 H, dd, J = 8.4, 10.8 Hz), 4.26 (1 H, q, J = 8.4 Hz), 3.81 (1 H, dd, J = 10.8, 8.1 Hz), 3.63 (1 H, dd, J = 16.8, 8.0 Hz), 3.25 (1 H, dd, J = 16.8, 8.9 Hz). 13

[001147] C NMR (DMSOd6): 175.9, 163.4, 163.3, 161.7, 161.6, 160.8, 145.8, 144.9, 144.8, 144.8, 121.2, 111, 111, 110.9, 110.8, 102.9, 102.8, 102.6, 51, 45.7, 31.4.

[001148] Example 46: (S) -1- (hydroxymethyl) -6- (2,3,5,6-tetrafluorophenyl) - 6,7-dihydro-2H-pyrrolo [1,2-c] imidazole- 3 (5H) -thione

[001149] To a stirred solution of 6- (2,3,5,6-tetrafluorophenyl) -3-thioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazole- (S) -ethyl 1-carboxylate (analogous to Example 43, step 7) (0.08 g, 0.222 mmol) in dry diethyl ether (2 ml) and dry tetrahydrofuran (1 ml) was added dropwise , 2.4 M suspension of lithium and aluminum hydride (0.102 mL, 0.244 mmol) in tetrahydrofuran with cooling with external cold water bath. The reaction was stirred in the cold for 30 min, then mitigated with 2 M HCl to pH = 1-2. After that, the mixture was diluted with dichloromethane (about 5 ml), the insoluble material was collected, washed with water and dichloromethane, respectively. The wet filter cake was dissolved in a mixture of ethanol and dichloromethane with heating and then filtered. The filtrate was evaporated to dryness to give (S) -1- (hydroxymethyl) -6- (2,3,5,6-tetrafluorophenyl) -6,7-dihydro-2H-pyrrole [1,2- c ] imidazole-3 (5H) -thione as an off-white solid. (Yield: 0.026 g, 36%).

[001150] 1H NMR (DMSOd6): 11.85 (1 H, br s), 7.86 (1 H, m), 5.07 (1 H, br t, J = 5.1 Hz), 4 , 50 (1 H, quin, J = 8.5 Hz), 4.21 (2 H, br d, J = 4.7 Hz), 4.18 (1 H, br dd, J = 11.4, 9.4 Hz), 3.78 (1 H, dd, J = 11.6, 7.6 Hz), 3.33 (1 H, m), 2.96 (1 H, br dd, J = 15 , 8, 8.0 Hz). 13

[001151] C NMR (DMSOd6): 155.6, 146.4, 146.3, 146.3, 145.3, 145.2, 144.7, 143.7, 143.6, 128.8, 120.5, 120.4, 120.4, 120.3, 105.9, 105.7, 105.6, 53.1, 48.4, 35.7, 29.

[001152] Example 47: (S) -1- (methylsulfonylmethyl) -6- (2,3,5,6-tetrafluorophenyl) -6,7-dihydro-2H-pyrrolo [1,2-c] imidazole- 3 (5H) -thione

[001153] Step 1: 2- (2- (methylsulfonyl) acetyl) -4- (2,3,5,6-

(4S) -tert-butyl tetrafluorophenyl) pyrrolidine-1-carboxylate

[001154] To a solution of (4S) -1- (tert-butoxycarbonyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-2-carboxylic acid (0.5 g, 1.376 mmol) (analogous to Example 44, step 9) in dry tetrahydrofuran (5 ml) di (1H-imidazol-1-yl) methanone (0.223 g, 1.376 mmol) was added at room temperature and the mixture was stirred for 30 min. Thereafter, a 1.6 M solution of methyl lithium (4.30 mL, 6.88 mmol) in diethyl ether was added to a solution of dimethylsulfone (0.648 g, 6.88 mmol) in dry tetrahydrofuran (5 ml) at room temperature and the mixture was stirred for 15 min before adding the imidazolid solution previously prepared with stirring and cooling with ice water bath. The mixture was stirred for 30 min in the cold, then blended with 2 M HCl (3.44 ml, 6.88 mmol) and extracted with diethyl ether (about 15 ml). The organic phase was dried over MgSO4) concentrated under reduced pressure and chromatographed (ethyl acetate - petroleum ether; 4: 1, then 2: 1) to give 2- (2- (methylsulfonyl) acetyl) -4- (2, 3,5,6-tetrafluorophenyl) (4S) -tert-butyl pyrrolidine-1-carboxylate as a colorless oil. (Yield: 0.45 g, 74%).

[001155] Step 2: 2- (methylsulfonyl) -1 - ((4S) -4- (2,3,5,6- tetrafluorophenyl) pyrrolidin-2-yl) ethanone hydrochloride

[001156] To a stirred solution of 2- (2- (methylsulfonyl) acetyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate (4S) -tert-butyl (0.41 g , 0.933 mmol) in 4 M HCl (4.67 mL, 18.66 mmol) in dioxane was stirred at room temperature for 3 h. The mixture was then diluted with a mixture of diethyl ether (20 ml) and petroleum ether (5 ml), and aged for 30 min. The precipitate thus obtained was collected, washed with diethyl ether and petroleum ether and then dried under vacuum at 50 ° C to give 2- (methylsulfonyl) -1 - ((4S) -4- (2,3, 5,6- tetrafluorophenyl) pyrrolidin-2-yl) ethanone as a white powder. (Yield: 0.28 g, 80%).

[001157] Step 3: (S) -1 - ((methylsulfonyl) methyl) -6- (2,3,5,6-tetrafluorophenyl) -6,7-dihydro-2H-pyrrole [1,2-c ] imidazole-3 (5H) -thione

[001158] A hydrochloride solution of 2- (methylsulfonyl) -1 - ((4S) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidin-2-yl) ethanone (0.27 g, 0.719 mmol) , 6 M HCl (0.060 ml, 0.359 mmol) and potassium thiocyanate (0.077 g, 0.790 mmol) in a mixture of ethanol (4 ml) and water (4 ml) was stirred under reflux for 30 min. The mixture was then cooled to room temperature, the resulting solid was collected, washed with water and dried under vacuum at 50 ° C to give (S) -1- (methylsulfonylmethyl) -6- (2,3,5,6- tetrafluorophenyl) -6,7-dihydro-2H-pyrrolo [1,2-c] imidazole-3 (5H) - as a white powder. (Yield: 0.21 g, 77%).

[001159] 1H NMR (DMSOd6): 12.08 (1 H, s), 7.86 (1 H, m), 4.57 (1 H, quin, J = 8.4 Hz), 4.30 (2 H, m), 4.23 (1 H, dd, J = 11.6, 9.2 Hz), 3.83 (1

H, dd, J = 11.7, 7.5 Hz), 3.38 (1 H, dd, J = 16.3, 9.4 Hz), 2.99 (1 H, dd, J = 7, 7, 16.4 Hz), 2.97 (3 H, s). 13

[001160] C NMR (DMSOd6): 156.6, 146.4, 146.3, 146.3, 145.2, 144.8, 144.7, 144.6, 143.6, 132.9, 120.5, 120.4, 120.3, 108, 105.9, 105.8, 105.6, 50.1, 49, 39.6, 35.6, 29.5.

[001161] Example 48: (5aS, 6aR) -5a- (2,5-difluorophenyl) -1-phenethyl-5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001162] Step 1 1- (2,5-difluorophenyl) -4- (methoxy (methyl) carbamoyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (1S, 5R) -tert-butyl

[001163] To a stirred solution of (1R, 5S) -3- (tert-butoxycarbonyl) -5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-2-carboxylic (3 g, 8.84 mmol) (analogous to Example 44, step 9) in dry dichloromethane (30 mL) 1,1'-carbonyldiimidazole (1.720 g, 10.61 mmol) was added in parts at room temperature under nitrogen and the mixture was stirred for 1 h. After that, N, O-dimethylhydroxylamine hydrochloride (1.035 g, 10.61 mmol) was added in one part and the resulting suspension was stirred overnight. The mixture was then washed with water, the organic phase was dried over MgSO4, filtered and evaporated to dryness. The light yellow oil thus obtained was purified by chromatography (petroleum ether - ethyl acetate; 4: 1, then 2: 1). The product was isolated as a light yellow foam. (Yield: 2.21 g, 59%).

[001164] Step 2 1- (2,5-difluorophenyl) -4- (3-phenylpropanoyl) -3-azabicyclo [3.1.0] (1S, 5R) -tert-butyl hexane-3-carboxylate

[001165] To a stirred ice-cooled mixture of phenethylmagnesium bromide in dry diethyl ether (8 mL) (prepared from (2-Bromoethyl) benzene (0.446 mL, 3.27 mmol) and magnesium shavings (0.165 g, 6.80 mmol)) a solution of 1- (2,5-difluorophenyl) -4- (methoxy (methyl) carbamoyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate was added dropwise (1S, 5R) -tert-butyl (1 g, 2.62 mmol) in dry tetrahydrofuran (5 mL) below 10 ° C. The reaction mixture was stirred at room temperature for 24 h. The mixture was then cooled to 0 ° C and 2M HCl was added carefully. The phases were separated and the organic phase was dried over MgSO4, filtered and evaporated to dryness. The resulting light yellow oil was purified by chromatography (petroleum ether - ethyl acetate; 9: 1, 4: 1, then 2: 1). (Yield: 0.34 g, 30%).

[001166] Step 3 1 - ((1R, 5S) -5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexan-2-yl) -3-phenylpropan-1-one hydrochloride

[001167] A solution of 1- (2,5-difluorophenyl) -4- (3-phenylpropanoyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate of (1S, 5R) -tert-butyl (340 mg , 0.795 mmol) in 4 M HCl in dioxane (1.59 mL, 6.36 mmol) was stirred at room temperature for 2 h. The solvent was removed by evaporation and the oil thus obtained was used without purification. (Yield: 0.289 g, 100%).

[001168] Step 4 (5aS, 6aR) -5a- (2,5-difluorophenyl) -1-phenethyl-5,5a, 6,6a- tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole -3 (2H) -thion

[001169] To a stirred hydrochloride solution of 1 - ((1R, 5S) -5- (2,5-difluorophenyl) -3-azabicyclo [3.1.0] hexan-2-yl) -3-phenylpropan-1- one (289 mg, 0.794 mmol) in a mixture of ethanol (3 mL) and water (3 mL) was added potassium thiocyanate (0.085 mL, 0.874 mmol) followed by addition of cc HCl. (0.033 mL, 0.397 mmol). The solution was heated to reflux and for 30 min. The mixture was then cooled to room temperature and the ethanol was removed by evaporation. The precipitated oil was extracted from the aqueous phase with dichloromethane. The organic phase was dried over MgSO4, filtered and evaporated to dryness. The light yellow foam thus obtained was purified by chromatography (petroleum ether - ethyl acetate; 1: 1), then 1: 2) to leave a yellow foam. (Yield: 0.11 g, 34%).

[001170] 1H NMR (DMSOd6): 11.78 (1 H, s), 7.29 (3 H, m), 7.20 (5 H, m), 4.03 (1 H, d, J = 12.2 Hz), 3.76 (1 H, d, J = 12.2 Hz), 2.88 (2 H, m), 2.70 (3 H, m), 1.53 (1 H , dd, J = 8.2, 5.3 Hz), 0.96 (1 H, t, J = 4.8 Hz). 13

[001171] C NMR (DMSOd6): 158.8, 158.8, 158.6, 158.6, 157.2, 157, 157, 155.7, 140.8, 130.5, 128.8, 128.7, 128.6, 128.6, 128.5, 128.4, 128.3, 128.3, 128.2, 128.2, 126, 118.7, 117.2, 117.1, 117, 117, 116.8, 116.8, 116.7, 116.7, 115.9, 115.8, 115.7, 115.7, 51.3, 51.3, 33.9, 32, 4, 25.9, 22.4, 20.5.

[001172] Example 49: (5aS, 6aR) -5a- (2,5-difluorophenyl) -1- (3-phenylpropyl) -5.5a, 6.6a-tetrahydrocyclopropa [3,4] pyrrole [1, 2-c] imidazole-

3 (2H) -thione

[001173] The compound was prepared analogously to Example 48 from 1- (2,5-difluorophenyl) -4- (methoxy (methyl) carbamoyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (1S, 5R) -tert-butyl and (3-phenylpropyl) magnesium bromide. The product was isolated as a yellow foam.

[001174] 1H NMR (DMSOd6): 11.71 (1 H, s), 7.28 (3 H, br t, J = 6.9 Hz), 7.24-7.14 (4 H, m ), 4.07 (1 H, br d, J = 11.9 Hz), 3.79 (1 H, d, J = 12.0 Hz), 2.85 (1 H, dd, J = 8, 1, 4.2 Hz), 2.61 (2 H, br t, J = 7.6 Hz), 2.42 (2 H, m), 1.91 (2 H, m), 1.64 ( 1 H, dd, J = 8.1, 5.4 Hz), 1.17 (1 H, br t, J = 4.7 Hz). 13

[001175] C NMR (DMSOd6): 158.8, 158.7, 158.7, 157.2, 157.1, 157.1, 155.8, 141.5, 130.2, 128.8, 128.8, 128.7, 128.7, 128.4, 128.3, 125.8, 119.1, 117.2, 117.1, 117, 116.9, 116.9, 116.8, 116.7, 115.9, 115.8, 115.7, 115.6, 51.3, 51.3, 34.4, 32.5, 29.2, 23.6, 22.5, 20, 6.

[001176] Example 50: (5aS, 6aR) -5a- (3,5-difluorophenyl) -1- (hydroxymethyl) -5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1,2- c] imidazole-3 (2H) -thione

[001177] Step 1 4- (1S, 5R) -tert-butyl 4- (cyano (hydroxy) methyl) -1- (3,5-difluorophenyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate

[001178] To a stirred solution of 1- (3,5-difluorophenyl) -4-formyl-3-azabicyclo [3.1.0] hexane-3-carboxylate (1S, 5R) -tert-butyl (0.500 g, 1.546 mmol) (analogous to Example 39, step 8) in a mixture of tetrahydrofuran (3.4 ml) and water (1.72 ml) potassium cyanide (0.121 g, 1.856 mmol) was added followed by the addition of cc HCl . (0.127 ml, 1.546 mmol). The reaction was stirred at room temperature overnight. The mixture was then extracted with dichloromethane, washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure to give the product as a yellow oil. (Yield: 0.554 g, 87%).

[001179] Step 2 1- (3,5-difluorophenyl) -4- (2-ethoxy-1-hydroxy-2-oxoethyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (1S, 5R) -tert-butyl

[001180] A solution of 4- (cyano (hydroxy) methyl) -1- (3,5-difluorophenyl) - 3-azabicyclo [3.1.0] hexane-3-carboxylate (1S) -tert-butyl (0.554 g , 1.581 mmol) in 2M HCl (11.86 mL, 23.72 mmol) was refluxed for 20 h. The mixture was then cooled to room temperature and the precipitated brown solid was removed by filtration. The filtrate was evaporated to dryness and then azeotroped twice with ethanol. The residue thus obtained was dissolved in ethanol (9 ml) and,

then, treated with 4 M HCl in dioxane (3.95 mL, 15.81 mmol). The reaction mixture was refluxed for 2 h, then cooled to room temperature and evaporated twice with ethanol. The resulting residue was dissolved in ethanol (11 ml), neutralized to pH = 6-7 by adding triethylamine (0.22 ml, 1.581 mmol) followed by adding di-tert-butyl dicarbonate (0.345 g, 1.581 mmol) . The reaction was stirred at room temperature overnight. After that, the mixture was concentrated under reduced pressure (water bath <40 ° C). The residue was mitigated with water and extracted with dichloromethane. The organic phase was dried over MgSO4, filtered and concentrated. The crude material was purified by chromatography (8% ethyl acetate in petroleum ether). The product was isolated as a pale yellow oil. (Yield: 0.21 g, 33%).

[001181] Step 3 2 - ((1R, 5S) -5- (3,5-difluorophenyl) -3-azabicyclo [3.1.0] hexan-2-yl) -2,2-dihydroxyacetate ethyl hydrochloride

[001182] To a stirred solution of 1- (3,5-difluorophenyl) -4- (2-ethoxy-1-hydroxy-2-oxoethyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (1S ) -tert-butyl (0.210 g, 0.528 mmol) in dichloromethane (5.3 mL) Dess-Martin periodinane (3-oxo-1λ5-benzo [d] [1,2] iodaoxole-1,1 triacetate) was added , 1 (3H) -triyl) (0.224 g, 0.528 mmol) at room temperature. The reaction was stirred at room temperature for 4 h. The solvent was then removed under reduced pressure to give a light pink pastel. Chromatography (dichloromethane - methanol - aq. Ammonia) gave the product as a pale yellow oil. (Yield:

, 142 g, 68%).

[001183] Step 4 ethyl 2 - ((1R, 5S) -5- (3,5-difluorophenyl) -3-azabicyclo [3.1.0] hexan-2-yl) -2,2-dihydroxyacetate hydrochloride

[001184] A solution of 1- (3,5-difluorophenyl) -4- (2-ethoxy-2-oxoacetyl) - 3-azabicyclo [3.1.0] hexane-3-carboxylate of (1S) -tert-butyl ( 0.142 g, 0.359 mmol) in 4 M HCl in dioxane (1.796 mL, 7.18 mmol) was stirred at room temperature for 2.5 h. The mixture was then diluted with a mixture of diethyl ether (4 ml) and petroleum ether (1 ml), stirred for 30 min, after which the volatiles were removed by evaporation to give the product as a brown oil. (Yield: 0.126 g, 100%).

[001185] Step 5 5a- (3,5-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-1 -carboxylate (5aS, 6aR) - ethyl

[001186] To a stirred solution of 2 - ((5S) -5- (3,5-difluorophenyl) -3-azabicyclo [3.1.0] hexan-2-yl) -2,2-dihydroxyacetate hydrochloride ( 0.126 g, 0.360 mmol) in a mixture of ethanol (1.5 mL) and water (1.5 mL) was added HCl cc. (0.03 mL, 0.180 mmol) and potassium thiocyanate (0.039 g, 0.396 mmol) at room temperature. The reaction mixture was refluxed for 30 min and then cooled to room temperature. Stirring was continued overnight and then the resulting off-white precipitate was removed by filtration, washed with cold water and dried under vacuum. (Yield: 0.79 mg, 65%).

[001187] Step 6 (5aS, 6aR) -5a- (3,5-difluorophenyl) -1- (hydroxymethyl) - 5.5a, 6.6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c ] imidazole-3 (2H) -thione

[001188] To a stirred solution of 5a- (3,5-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] (5aS, 6aR) -ethyl imidazole-1-carboxylate (0.188 g, 0.559 mmol) in a mixture of dry diethyl ether (3.2 ml) and dry tetrahydrofuran (1.6 ml) was added dropwise , 2.4 M suspension of lithium aluminum hydride (0.256 ml, 0.615 mmol) in tetrahydrofuran with cooling with ice water bath. The reaction was stirred for 30 min at 0-5 ° C, mitigated with 0.5 M HCl to pH = 1-2 (about 5 ml) and then diluted with diethyl ether (about 10 ml). The resulting solid was collected, washed with water and dried under vacuum at 50 ° C to give a light yellow powder. (Yield: 0.038 g, 22%).

[001189] 1H NMR (DMSOd6): 11.75 (1 H, br s), 7.11 (3 H, m), 5.10 (1 H, br s), 4.25 (2 H, m ), 4.20 (1 H, d, J = 12.2 Hz), 4.03 (1 H, d, J = 12.0 Hz), 3.02 (1 H, dd, J = 8.3 , 4.3 Hz), 1.69 (1 H, dd, J = 8.4, 5.3 Hz), 1.17 (1 H, t, J = 4.8 Hz). 13

[001190] C NMR (DMSOd6): 163.4, 163.3, 161.8, 161.7, 156.7, 144.9, 144.8, 144.8, 131.4, 119.8, 110, 110, 109.9, 109.8, 102.3, 102.1, 101.9, 53.1, 50.7, 36.3, 25.4, 22.9.

[001191] Example 51: 2 - ((5aS, 6aR) -5a- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocycloprop acid [ 3.4] pyrrole [1,2-c] imidazol-1-yl) acetic

[001192] The compound was prepared in an analogous manner to Example 2 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (3-bromo-2,6-difluorophenyl) -3-azabicyclo [3.1 .0] hexane-2-carboxylic. The product was isolated as a yellow solid.

[001193] 1H NMR (DMSOd6): 12.63 (1 H, br s), 11.72 (1 H, br s), 7.75 (1 H, td, J = 8.5, 5.8 Hz), 7.16 (1 H, td, J = 9.2, 1.0 Hz), 4.04 (1 H, d, J = 12.2 Hz), 3.74 (1 H, br d , J = 12.0 Hz), 3.49 (2 H, m), 2.77 (1 H, dd, J = 8.4, 4.3 Hz), 1.67 (1 H, dd, J = 8.4, 5.4 Hz), 1.24 (1 H, t, J = 5.0 Hz). 13

[001194] C NMR (DMSOd6): 170.8, 161.9, 161.9, 160.2, 160.2, 158.8, 158.8, 158.8, 157.2, 157.1, 133.1, 133, 131.9, 117.1, 117, 116.9, 113.5, 113.5, 113.4, 113.3, 113.3, 103.7, 103.7, 103, 6, 103.6, 51.5, 29.9, 26.5, 21.8, 21.2.

[001195] Example 52: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocycloprop acid [3, 4] pyrrole [1,2-c] imidazol-1-yl) acetic

[001196] The compound was prepared in an analogous manner to Example 2 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (5-chloro-2-fluorophenyl) - 3-azabicyclo [3.1.0 ] hexane-2-carboxylic. The product was isolated as a light yellow solid.

[001197] 1H NMR (DMSOd6): 12.60 (1 H, br s), 11.70 (1 H, s), 7.45 (1 H, dd, J = 6.5, 2.5 Hz ), 7.42 (1 H, ddd, J = 8.6, 4.3, 2.8 Hz), 7.30 (1 H, t, J = 9.4 Hz), 4.09 (1 H , br d, J = 12.0 Hz), 3.80 (1 H, d, J = 12.0 Hz), 3.47 (2 H, m), 2.88 (1 H, dd, J = 8.2, 4.1 Hz), 1.67 (1 H, dd, J = 8.2, 5.4 Hz), 1.12 (1 H, t, J = 4.8 Hz). 13

[001198] C NMR (DMSOd6): 170.8, 161.3, 159.6, 156.1, 132.1, 130.1, 130.1, 129.4, 129.3, 128.9, 128.8, 128.3, 128.3, 117.6, 117.4, 113, 51.6, 32.4, 29.9, 22.2, 20.6.

[001199] Example 53: 2 - ((5aS, 6aR) -5a- (3-chloro-5-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocycloprop acid [3, 4] pyrrole [1,2-c] imidazol-1-yl) acetic

[001200] The compound was prepared in an analogous manner to Example 2 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (3-chloro-5-fluorophenyl) - 3-azabicyclo [3.1.0 ] hexane-2-carboxylic. The product was isolated as a light yellow solid.

[001201] 1H NMR (DMSOd6): 12.60 (1 H, br s), 11.68 (1 H, s), 7.31 (1 H, dt, J = 8.7, 2.0 Hz ), 7.27 (1 H, t, J = 1.5 Hz), 7.22 (1 H, dt, J = 9.9, 1.9 Hz), 4.21 (1 H, d, J = 12.0 Hz), 4.03 (1 H, d, J = 12.2 Hz), 3.45 (2 H, m), 3.00 (1 H, dd, J = 8.4, 4 , 3 Hz), 1.69 (1 H, dd, J = 8.2, 5.3 Hz), 1.14 (1 H, t, J = 4.8 Hz). 13

[001202] C NMR (DMSOd6): 170.7, 163.1, 161.5, 156.3, 144.8, 144.7, 134.2, 134.1, 132, 123, 122.9, 114.3, 114.2, 112.9, 112.8, 112.8, 50.8, 36.1, 36.1, 29.9, 25.1, 22.6.

[001203] Example 54: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) ethyl acetate

[001204] The compound was prepared in an analogous way to Example 2 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (5-chloro-2-fluorophenyl) - 3-azabicyclo [3.1.0 ] hexane-2-carboxylic. The product was isolated as an off-white foam.

[001205] 1H NMR (DMSOd6): 11.73 (1 H, s), 7.46 (1 H, dd, J = 6.5, 2.6 Hz), 7.43 (1 H, ddd, J = 8.6, 4.3, 2.8 Hz), 7.30 (1 H, t, J = 9.4 Hz), 4.11 (2 H, q, J = 7.1 Hz), 4.09 (1H, d, J = 12.2 Hz), 3.81 (1 H, d, J = 12.2 Hz), 3.57 (2 H, m), 2.87 (1 H, dd, J = 8.3, 4.2 Hz), 1.68 (1 H, dd, J = 8.4, 5.4 Hz), 1.21 (3 H, t, J = 7.1 Hz ), 1.13 (1 H, t, J = 4.8 Hz).

[001206] C NMR (DMSOd6): 169.2, 161.3, 159.6, 156.2, 132.3, 130.2, 130.1, 129.4, 129.3, 128.8, 128.7, 128.3, 128.3, 117.6, 117.4, 112.3, 60.7, 51.6, 51.6, 32.4, 29.8, 22.1, 20, 6, 14.1.

[001207] Example 55: 2 - ((5aS, 6aR) -5a- (3-chloro-5-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) ethyl acetate

[001208] The compound was prepared in an analogous manner to Example 2 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (3-chloro-5-fluorophenyl) - 3-azabicyclo [3.1.0 ] hexane-2-carboxylic. The product was isolated as a white solid.

[001209] 1H NMR (DMSOd6): 11.72 (1 H, s), 7.32 (1 H, dt, J = 8.7, 2.0 Hz), 7.28 (1 H, t, J = 1.5 Hz), 7.23 (1 H, dt, J = 9.9, 2.0 Hz), 4.21 (1 H, d, J = 12.2 Hz), 4.11 ( 2 H, q, J = 7.0 Hz), 4.04 (1 H, d, J = 12.2 Hz), 3.54 (2 H, m), 2.99 (1 H, dd, J = 8.4, 4.4 Hz), 1.70 (1 H, dd, J = 8.4, 5.3 Hz), 1.21 (3 H, t, J = 7.0 Hz), 1 , 15 (1 H, t, J = 4.8 Hz). 13

[001210] C NMR (DMSOd6): 169.2, 163.1, 161.5, 156.4, 144.7, 144.7, 134.2, 134.1, 132.3, 123, 123, 114.4, 114.2, 112.9, 112.8, 112.1, 60.7, 50.9, 36.1, 36.1, 29.8, 25, 22.7, 14.1.

[001211] Example 56: (2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3, 4] pyrrolo [1,2-c] imidazol-1-yl) acetamide

[001212] To a stirred solution of 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocycloprop acid [ 3.4] pyrrole [1,2-c] imidazol-1-yl) acetic (Example 52) (630 mg, 1.860 mmol) in anhydrous dichloromethane (11 mL) 1,1'-Carbonyldiimidazole (362 mg, 2,232) was added mmol) and the reaction was stirred for 30 min at room temperature. After that, 7 M ammonia (0.53 ml, 3.72 ml) in methanol was added and the mixture was stirred for 3 h at room temperature. The solvent was then evaporated and the brown oil obtained was separated by column chromatography (dichloromethane - methanol). Trituration in a mixture of dichloromethane - diethyl ether - petroleum ether gave the title product as a dark yellow solid.

[001213] 1H NMR (DMSOd6): 11.64 (1 H, s), 7.46 (1 H, dd, J = 6.6, 2.6 Hz), 7.43 (1 H, ddd, J = 8.7, 4.3, 2.7 Hz), 7.37 (1 H, br s), 7.30 (1 H, t, J = 9.5 Hz), 7.03 (1 H , m), 4.07 (1 H, d, J = 12.0 Hz), 3.79 (1 H, d, J = 12.0 Hz), 3.27 (2 H, m), 2, 85 (1 H, dd, J = 8.4, 4.3 Hz), 1.64 (1 H, dd, J = 8.4, 5.3 Hz), 1.17 (1 H, t, J = 4.8 Hz). 13

[001214] C NMR (DMSOd6): 169.9, 161.2, 159.6, 155.9, 131.8, 130.1, 130.1, 129.3, 129.3, 129, 128, 9, 128.3, 128.3, 117.6, 117.4, 114, 51.6, 32.3, 31.2, 22.1, 20.7.

[001215] Example 57: 2 - ((5aS, 6aR) -5a- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) acetamide

[001216] The compound was prepared analogously to Example 56 from 2 - ((5aS, 6aR) -5a- (3-bromo-2,6-difluorophenyl) -3-thioxo- 2,3,5 acid, 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 51). The product was isolated as a yellow solid.

[001217] 1H NMR (DMSOd6): 11.67 (1 H, m), 7.74 (1 H, td, J = 8.4, 5.9 Hz), 7.39 (1 H, br s ), 7.15 (1 H, td, J = 9.2, 1.2 Hz), 7.04 (1 H, br s), 4.02 (1 H, d, J = 12.2 Hz) , 3.72 (1 H, d, J = 12.2 Hz), 3.29 (2 H, m), 2.74 (1 H, dd, J = 8.4, 4.4 Hz), 1 , 64 (1 H, dd, J = 8.2, 5.4 Hz), 1.28 (1 H, br t, J = 4.9 Hz). 13

[001218] C NMR (DMSOd6): 169.9, 161.9, 161.9, 160.2, 160.2, 158.8, 158.8, 157.2, 157.1, 155.8, 133, 133, 131.5, 117.2, 117.1, 117, 114.4, 113.5, 113.5, 113.4, 113.3, 103.7, 103.7, 103.6, 103.6, 51.4, 31.2, 26.4, 21.7, 21.3.

[001219] Example 58: 2 - ((5aS, 6aR) -5a- (3-chloro-5-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) acetamide

[001220] The compound was prepared in an analogous manner to Example 56 from 2 - ((5aS, 6aR) -5a- (3-chloro-5-fluorophenyl) -3-thioxo- 2,3,5,5a acid, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 53). The product was isolated as a beige solid.

[001221] 1H NMR (DMSOd6): 11.62 (1 H, s), 7.35 (1 H, br s), 7.31 (1 H, dt, J = 8.7, 2.1 Hz ), 7.28 (1 H, t, J = 1.6 Hz), 7.23 (1 H, dt, J = 10.0, 1.9 Hz), 7.05 (1 H, br s) , 4.19 (1 H, d, J = 12.0 Hz), 4.01 (1 H, d, J = 12.0 Hz), 3.25 (2 H, m), 2.95 (1 H, dd, J = 8.4, 4.3 Hz), 1.67 (1 H, dd, J = 8.4, 5.3 Hz), 1.19 (1 H, t, J = 4, 8 Hz). 13

[001222] C NMR (DMSOd6): 169.9, 163.1, 161.5, 156.1, 144.9, 144.9, 134.2, 134.1, 131.9, 123, 123, 114.3, 114.1, 113.7, 112.9, 112.8, 50.9, 36.1, 36.1, 31.2, 24.9, 22.8

[001223] Example 59: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) ethyl acetate

[001224] The compound was prepared in an analogous manner to Example 2 from (4S) -1- (tert-butoxycarbonyl) -4- (3-bromo-2,6-difluorophenyl) pyrrolidine-2-carboxylic acid and isolated as a yellow solid.

[001225] 1H NMR (DMSOd6): 11.81 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.16 (1 H, dt, J = 1.4, 9.4 Hz), 4.47 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.2, 9, 5 Hz), 4.09 (2 H, q, J = 7.1 Hz), 3.73 (1 H, dd, J = 11.6, 7.8 Hz), 3.50 (2 H, s ), 3.27 (1 H, dd, J = 15.8, 9.4 Hz), 2.86 (1 H, dd, J = 15.8, 7.9 Hz), 1.19 (3 H , t, J = 7.1 Hz). 13

[001226] C NMR (DMSOd6): 169.1, 160.8, 160.8, 159.2, 159.1,

157.6, 157.5, 155.9, 155.9, 155.4, 132.5, 132.4, 129.9, 118.9, 118.7, 118.6, 113.8, 113, 8, 113.6, 113.6, 112.6, 104.1, 104.1, 103.9, 103.9, 60.7, 48.7, 35.6, 29.8, 29.3, 14.1.

[001227] Example 60: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) ethyl acetate

[001228] The compound was prepared in an analogous manner to Example 2 from (4R) -1- (tert-butoxycarbonyl) -4- (3-bromo-2,6-difluorophenyl) pyrrolidine-2-carboxylic acid and isolated as a yellow solid.

[001229] 1H NMR (DMSOd6): 11.81 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.16 (1 H, dt, J = 1.4, 9.6 Hz), 4.47 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.4, 9, 2 Hz), 4.09 (2 H, q, J = 7.0 Hz), 3.73 (1 H, dd, J = 11.6, 7.8 Hz), 3.50 (2 H, s ), 3.27 (1 H, dd, J = 16.0, 9.4 Hz), 2.86 (1 H, dd, J = 15.9, 8.0 Hz), 1.19 (3 H , t, J = 7.1 Hz). 13

[001230] C NMR (DMSOd6): 169.1, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.4, 132.5, 132.4, 129.9, 118.9, 118.7, 118.6, 113.8, 113.8, 113.6, 113.6, 112.6, 104.1, 104, 1, 103.9, 103.9, 60.7, 48.7, 35.6, 29.8, 29.2, 14.1.

[001231] Example 61: (R) -2- (6- (2,5-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole -1-yl) ethyl acetate

[001232] The compound was prepared analogously to Example 2 from (4R) -1- (tert-butoxycarbonyl) -4- (2,5-difluorophenyl) pyrrolidine-2-carboxylic acid and isolated as a white solid.

[001233] 1H NMR (DMSOd6): 11.82 (1 H, s), 7.29 (1 H, dt, J = 4.7, 9.5 Hz), 7.26 (1 H, m) , 7.19 (1 H, m), 4.22 (1 H, quin, J = 7.8 Hz), 4.14 (1 H, dd, J = 11.3, 7.9 Hz), 4 .09 (2 H, q, J = 7.0 Hz), 3.74 (1 H, dd, J = 11.3, 7.5 Hz), 3.53 (2 H, m), 3.22 (1 H, dd, J = 15.5, 8.0 Hz), 2.86 (1 H, dd, J = 15.5, 7.8 Hz), 1.19 (3 H, t, J = 7.1 Hz). 13

[001234] C NMR (DMSOd6): 169.2, 159.1, 159, 157.5, 157.5, 157.1, 157.1, 155.6, 155.5, 155.5, 130, 1, 130, 130, 129.9, 129.8, 117.2, 117.1, 117, 116.9, 115.5, 115.4, 115.3, 115.3, 115.2, 115, 2, 115.1, 115, 113.1, 60.7, 49.4, 40.3, 29.8, 29.6, 14.1.

[001235] Example 62: (S) -2- (6- (5-bromo-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) ethyl acetate

[001236] The compound was prepared analogously to Example 2 from (4S) -1- (tert-butoxycarbonyl) -4- (5-bromo-2-fluorophenyl) pyrrolidine-2-carboxylic acid and isolated as a solid orange.

[001237] 1H NMR (DMSOd6): 11.80 (1 H, s), 7.58 (1 H, dd, J = 6.6, 2.5 Hz), 7.53 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.23 (1 H, dd, J = 10.1, 8.8 Hz), 4.22 (1 H, quin, J = 7, 9 Hz), 4.14 (1 H, dd, J = 11.2, 8.1 Hz), 4.09 (2 H, q, J = 7.2 Hz), 3.75 (1 H, dd , J = 11.3, 7.5 Hz), 3.52 (2 H, m), 3.22 (1 H, dd, J = 15.6, 8.2 Hz), 2.87 (1 H , dd, J = 15.6, 7.9 Hz), 1.19 (3 H, t, J = 7.1 Hz). 13

[001238] C NMR (DMSOd6): 169.2, 160.3, 158.7, 155.6, 131.9, 131.8, 131.4, 131.3, 130.7, 130.6, 129.7, 118, 117.9, 116.5, 116.5, 113, 60.7, 49.3, 40.4, 29.8, 29.5, 14.1.

[001239] Example 63: (R) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) ethyl acetate

[001240] The compound was prepared in an analogous manner to Example 2 from (4R) -1- (tert-butoxycarbonyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-2-carboxylic acid and isolated as a light cream powder.

[001241] 1H NMR (DMSOd6): 11.83 (1 H, s), 7.86 (1 H, m), 4.51 (1 H, quin, J = 8.5 Hz), 4.19 (1 H, dd, J = 11.6, 9.1 Hz), 4.09 (2 H, q, J = 7.2 Hz), 3.79 (1 H, dd, J = 11.7, 7.6 Hz), 3.51 (2 H, s), 3.30 (1 H, dd, J = 16.0, 9.4 Hz), 2.91 (1 H, dd, J = 15, 9, 7.8 Hz), 1.19 (3 H, t, J = 7.1 Hz). 13

[001242] C NMR (DMSOd6): 169.1, 155.5, 146.4, 146.3, 146.2, 145.3, 145.2, 144.7, 144.6, 143.7, 143.6, 129.6, 120.5, 120.4, 120.3, 112.7, 105.9, 105.7, 105.6, 60.6, 48.6, 35.7, 29, 8, 29.1, 14.

[001243] Example 64: (R) -2- (6- (5-chloro-2-fluorophenyl) -3-thioxo-2,5,6,7-

tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethyl acetate

[001244] The compound was prepared analogously to Example 2 from (4R) -1- (tert-butoxycarbonyl) -4- (5-chloro-2-fluorophenyl) pyrrolidine-2-carboxylic acid and isolated as a solid pale yellow.

[001245] 1H NMR (DMSOd6): 11.78 (1 H, s), 7.45 (1 H, dd, J = 6.5, 2.6 Hz), 7.40 (1 H, ddd, J = 8.8, 4.4, 2.7 Hz), 7.29 (1 H, dd, J = 10.1, 8.9 Hz), 4.22 (1 H, quin, J = 7, 8 Hz), 4.15 (1 H, dd, J = 11.3, 8.1 Hz), 4.10 (2 H, q, J = 7.2 Hz), 3.75 (1 H, dd , J = 11.3, 7.5 Hz), 3.52 (2 H, m), 3.22 (1 H, dd, J = 15.5, 8.1 Hz), 2.88 (1 H , dd, J = 15.6, 7.8 Hz), 1.19 (3 H, t, J = 7.0 Hz). 13

[001246] C NMR (DMSOd6): 169.1, 159.8, 158.1, 155.6, 130.3, 130.2, 129.7, 128.9, 128.8, 128.5, 128.5, 128.4, 128.4, 117.6, 117.4, 113, 60.7, 49.3, 40.3, 29.8, 29.5, 14.

[001247] Example 65: (R) -2- (6- (2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole -1-yl) ethyl acetate

[001248] The compound was prepared in an analogous manner to Example 2 from (4R) -1- (tert-butoxycarbonyl) -4- (2,6-difluorophenyl) pyrrolidine-2-carboxylic acid and isolated as an orange solid.

[001249] 1H NMR (DMSOd6): 11.80 (1 H, s), 7.41 (1 H, tt, J = 8.4, 6.6 Hz), 7.13 (2 H, m) , 4.43 (1 H, quin, J = 8.7 Hz), 4.16 (1 H, dd, J = 9.2, 11.3 Hz), 4.09 (2 H, q, J = 7.0 Hz), 3.73 (1 H, dd, J = 11.4, 8.2 Hz), 3.50 (2 H, s), 3.25 (1 H, dd, J = 15, 7, 9.2 Hz), 2.86 (1 H, dd, J = 15.7, 8.5 Hz), 1.19 (3 H, t, J = 7.1 Hz). 13

[001250] C NMR (DMSOd6): 169.1, 161.6, 161.5, 160, 159.9, 155.4, 130, 129.8, 129.8, 129.7, 116.6, 116.5, 116.4, 112.6, 112.2, 112.2, 112.1, 112.1, 60.6, 48.7, 35.2, 29.8, 29.3, 14.

[001251] Example 66: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) -1- morpholinoetan-1-one

[001252] The compound was prepared analogously to Example 37 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (5-chloro-2-fluorophenyl) - 3-azabicyclo [3.1.0 ] hexane-2-carboxylic and isolated as a greenish solid.

[001253] 1H NMR (DMSOd6): 11.64 (1 H, s), 7.45 (1 H, dd, J = 2.7, 6.5 Hz), 7.43 (1 H, ddd, J = 8.6, 4.4, 2.7 Hz), 7.30 (1 H, dd, J = 9.9, 8.7 Hz), 4.08 (1 H, d, J = 12, 0 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.57 (6 H, m), 3.49 (2 H, m), 3.46 (2 H, m) , 2.78 (1 H, dd,

J = 8.4, 4.3 Hz), 1.69 (1 H, dd, J = 8.3, 5.4 Hz), 1.11 (1 H, t, J = 4.8 Hz). 13

[001254] C NMR (DMSOd6): 166.9, 161.3, 159.6, 156, 131.8, 130.2, 130.2, 129.4, 129.3, 128.8, 128, 7, 128.3, 128.3, 117.6, 117.4, 113.7, 66, 54.9, 51.6, 45.7, 41.8, 32.4, 29, 22.1, 20.7.

[001255] Example 67: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) -N- isopropylacetamide

[001256] The compound was prepared analogously to Example 37 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (5-chloro-2-fluorophenyl) - 3-azabicyclo [3.1.0 ] hexane-2-carboxylic and isolated as a light yellow solid.

[001257] 1H NMR (DMSOd6): 11.69 (1 H, s), 7.88 (1 H, d, J = 7.6 Hz), 7.45 (1 H, dd, J = 2, 6, 6.5 Hz), 7.43 (1 H, ddd, J = 8.5, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 9.8, 8, 8 Hz), 4.07 (1 H, d, J = 12 Hz), 3.83 (1 H, oct, J = 7.3 Hz), 3.79 (1 H, d, J = 12 , 2 Hz), 3.25 (2 H, m), 2.80 (1 H, dd, J = 8.4, 4.3 Hz), 1.66 (1 H, dd, J = 8.4 , 5.3 Hz), 1.13 (1 H, t, J = 4.8 Hz), 1.06 (6 H, d, J = 6.6 Hz). 13

[001258] C NMR (DMSOd6): 166.7, 161.2, 159.6, 155.8, 131.6, 130.2, 130.1, 129.3, 129.3, 128.9, 128.8, 128.3, 128.3, 117.6, 117.4, 114.1, 51.5, 51.5, 40.7, 32.3, 31.5, 22.4, 22, 3, 22, 20.8.

[001259] Example 68: 2 - ((5aS, 6aR) -5a- (3-chloro-5-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) -N-methylacetamide

[001260] The compound was prepared analogously to Example 37 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (3-chloro-5-fluorophenyl) - 3-azabicyclo [3.1.0 ] hexane-2-carboxylic and isolated as a light yellow solid.

[001261] 1H NMR (DMSOd6): 11.62 (1 H, s), 7.78 (1 H, q, J = 4.5 Hz), 7.31 (1 H, dt, J = 8, 7, 1.9 Hz), 7.28 (1 H, t, J = 1.5 Hz), 7.23 (1 H, dt, J = 10.0, 1.8 Hz), 4.19 ( 1 H, d, J = 12.2 Hz), 4.02 (1 H, d, J = 12.0 Hz), 3.27 (2 H, m), 2.93 (1 H, dd, J = 8.3, 4.3 Hz), 2.60 (3 H, d, J = 4.5 Hz), 1.67 (1 H, dd, J = 8.4, 5.3 Hz), 1 , 20 (1 H, t, J = 4.8 Hz). 13

[001262] C NMR (DMSOd6): 168.2, 163.1, 161.4, 156.2, 144.9, 144.8, 134.2, 134.1, 132, 123, 123, 114, 3, 114.1, 113.4, 112.9, 112.8, 50.9, 36, 36, 31.3, 24.9, 22.8.

[001263] Example 69: 2 - ((5aS, 6aR) -5a- (3-chloro-5-fluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) -N, N-dimethylacetamide

[001264] The compound was prepared in an analogous way to Example 37 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (3-chloro-5-fluorophenyl) - 3-azabicyclo [3.1.0 ] hexane-2-carboxylic and isolated as a yellow solid.

[001265] 1H NMR (DMSOd6): 11.58 (1 H, s), 7.31 (1 H, dt, J = 8.7, 2.1 Hz), 7.27 (1 H, t, J = 1.6 Hz), 7.22 (1 H, dt, J = 10.0, 2.0 Hz), 4.20 (1 H, d, J = 12 Hz), 4.03 ( 1 H, d, J = 12.0 Hz), 3.52 (2 H, s), 3.02 (3 H, s), 2.90 (1 H, dd, J = 8.4, 4, 4 Hz), 2.85 (3 H, s), 1.68 (1 H, dd, J = 8.3, 5.2 Hz), 1.13 (1 H, t, J = 4.8 Hz ). 13

[001266] C NMR (DMSOd6): 167.9, 163.1, 161.5, 156.1, 144.8, 144.8, 134.2, 134.1, 131.6, 122.9, 122.9, 114.3, 114.1, 113.8, 112.9, 112.7, 50.8, 37, 36, 36, 35.1, 29.2, 25.1, 22.8.

[001267] Example 70: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - 1- (pyrrolidin-1-yl) ethan-1-one

[001268] The compound was prepared analogously to Example 37 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (5-bromo-2-fluorophenyl) -3-azabicyclo [3.1.0 ] hexane-2-carboxylic and isolated as a light yellow solid.

[001269] 1H NMR (DMSOd6): 11.61 (1 H, s), 7.59-7.53 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8 , 7 Hz), 4.07 (1 H, d, J = 12.0 Hz), 3.79 (1 H, d, J = 12.0 Hz), 3.48 (2 H, m), 3 , 46 (2 H, t, 6.9 Hz), 3.31 (2 H, t, J = 6.9 Hz), 2.79 (1 H, dd, J = 8.4, 4.3 Hz ), 1.90 (2 H, quin, J = 6.9 Hz), 1.78 (2 H, quin, J = 6.9 Hz), 1.67 (1 H, dd, J = 8.4 , 5.3 Hz), 1.10 (1 H, t br, J = 4.8

Hz).

[001270] 13C NMR (DMSOd6): 166.2, 161.8, 160.1, 155.9, 133, 133, 132.3, 132.2, 131.7, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 113.8, 51.6, 51.6, 46.1, 45.6, 32.2, 30.5, 25.6, 24, 22, 1, 20.7.

[001271] Example 71: (R) -N- (3- (dimethylamino) propyl) hydrochloride -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6, 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[001272] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a yellowish powder.

[001273] 1H NMR (DMSOd6): 11.78 (1 H, m), 10.33 (1 H, br s), 8.22 (1 H, br t, J = 5.5 Hz), 7 , 85 (1 H, m), 4.50 (1 H, quin, J = 8.5 Hz), 4.19 (1 H, br t, J = 10.3 Hz), 3.80 (1 H , m), 3.29 (3 H, m), 3.11 (2 H, q, J = 6.4 Hz), 3.01 (2 H, m), 2.91 (1 H, br dd , J = 15.7, 8.2 Hz), 2.71 (6 H, d, J = 4.5 Hz), 1.79 (2 H, m). 13

[001274] C NMR (DMSOd6): 168.1, 146.4, 146.4, 146.3, 145.4, 145.4, 145.3, 145.3, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.7, 144.6, 143.8, 143.7, 143.7, 143.7, 143.6, 143, 6, 129.5, 120.3, 120.2, 119.2, 114.7, 105.9, 105.8, 105.6, 54.4, 48.5, 42, 42, 35.9, 35.8, 31.5, 29.2, 24.1.

[001275] Example 72: (R) -N- (2-hydroxyethyl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[001276] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[001277] 1H NMR (DMSOd6): 10.98 (1 H, m), 7.98 (1 H, br t, J = 5.2 Hz), 7.84 (1 H, m), 4, 68 (1 H, br s), 4.48 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, br dd, J = 11.2, 9.5 Hz), 3, 77 (1 H, dd, J = 11.5, 8.0 Hz), 3.39 (2 H, br t, J = 5.9 Hz), 3.25 (3 H, m), 3.11 (2 H, q, J = 5.9 Hz), 2.89 (1 H, br dd, J = 15.8, 8.1 Hz). 13

[001278] C NMR (DMSOd6): 167.7, 155.2, 146.4, 146.3, 146.3, 145.4, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143, 6, 143.6, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.4, 105.9, 105.7, 105.6, 59.7, 48.4, 41.7, 35.8, 31.5, 29.1.

[001279] Example 73: (R) -N- (2-methoxyethyl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[001280] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light beige powder.

[001281] 1H NMR (DMSOd6): 11.74 (1 H, br s), 8.04 (1 H, br t, J = 5.1 Hz), 7.85 (1 H, m), 4 , 48 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 9.5, 11.3 Hz), 3.77 (1 H, dd, J = 11, 5, 8.0 Hz), 3.33 (2H, t, J = 5.4 Hz), 3.29-3.16 (8H, m), 2.88 (1 H, br dd, J = 15 , 9, 8.1 Hz). 13

[001282] C NMR (DMSOd6): 167.7, 155.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144, 6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.3, 105.9, 105.7, 105.6, 70.5, 57.8, 48.4, 38.6, 35.7, 31.4, 29.2.

[001283] Example 74: (S) -2- (6- (5-bromo-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -N-cyclopentylacetamide

[001284] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (5-bromo-2-fluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a pale brown solid.

[001285] 1H NMR (DMSOd6): 11.71 (1 H, s), 7.93 (1 H, br d, J = 7.0 Hz), 7.57 (1 H, dd, J = 6 , 7, 2.4 Hz), 7.53 (1 H, ddd, J = 8.7, 4.5, 2.5 Hz), 7.23 (1 H, dd, J = 10.3, 8 , 8 Hz), 4.20 (1 H, quin,

J = 7.8 Hz), 4.12 (1 H, dd, J = 11.2, 8.1 Hz), 3.97 (1 H, sxt, J = 6.9 Hz), 3.73 ( 1 H, dd, J = 11.3, 7.5 Hz), 3.21 (2 H, s), 3.17 (1 H, br dd, J = 15.5, 8.1 Hz), 2 , 83 (1 H, dd, J = 15.5, 7.8 Hz), 1.77 (2 H, m), 1.61 (2 H, m), 1.48 (2 H, m), 1.35 (2 H, m). 13

[001286] C NMR (DMSOd6): 167, 160.3, 158.7, 155.2, 131.9, 131.8, 131.4, 131.3, 130.8, 130.7, 128, 8, 118, 117.9, 116.5, 116.5, 114.8, 50.5, 49.2, 40.3, 32.2, 31.5, 29.7, 23.4.

[001287] Example 75: 2 - ((R) -6- (5-chloro-2-fluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[001288] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (5-chloro-2-fluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a green solid.

[001289] 1H NMR (DMSOd6): 11.72 (1 H, s), 8.22 (1 H, br d, J = 6.5 Hz), 7.45 (1 H, dd, J = 6 , 5, 2.6 Hz), 7.40 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.29 (1 H, dd, J = 10.1, 8 , 9 Hz), 4.21 (2 H, m), 4.13 (1 H, dd, J = 11.3, 8.1 Hz), 3.77 (1 H, m), 3.72 ( 2 H, m), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, dd, J = 8.9, 3.7 Hz), 3, 25 (2 H, s), 3.18 (1 H, dd, J = 15.4, 8.1 Hz), 2.84 (1 H, dd, J = 15.4, 7.8 Hz), 2.07 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m). 13

[001290] C NMR (DMSOd6): 167.6, 159.8, 158.2, 155.3, 130.4,

130.3, 129, 128.9, 128.8, 128.5, 128.5, 128.5, 128.4, 117.6, 117.4, 114.6, 72.4, 66.3, 49.8, 49.2, 40.3, 32, 31.3, 29.6.

[001291] Example 76: (R) -N-cyclopentyl-2- (6- (2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) acetamide

[001292] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,6-difluorophenyl) -3-thioxo-3 , 5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a pale gray solid.

[001293] 1H NMR (DMSOd6): 11.72 (1 H, s), 7.92 (1 H, br d, J = 7.2 Hz), 7.40 (1 H, m), 7, 13 (2 H, m), 4.41 (1 H, quin, J = 8.8 Hz), 4.14 (1 H, dd, J = 9.3, 11.3 Hz), 3.96 ( 1 H, sxt, J = 6.8 Hz), 3.71 (1 H, dd, J = 11.4, 8.4 Hz), 3.20 (2 H, s), 3.18 (1 H , dd, J = 9.2, 15.6 Hz), 2.84 (1 H, dd, J = 15.6, 8.6 Hz), 1.77 (2 H, m), 1.61 ( 2 H, m), 1.48 (2 H, m), 1.35 (2 H, m).

[001294] 13C NMR (DMSOd6): 167, 161.6, 161.6, 160, 159.9, 155.1, 129.8, 129.7, 129.7, 129, 116.6, 116, 4, 116.3, 114.5, 112.2, 112.2, 112.1, 112.1, 50.5, 48.6, 35.3, 32.2, 32.2, 31.5, 29.4, 23.4.

[001295] Example 77: 2 - ((R) -6- (2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole -1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[001296] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,6-difluorophenyl) -3-thioxo-3 , 5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a pale gray solid.

[001297] 1H NMR (DMSOd6): 11.73 (1 H, s), 8.21 (1 H, br d, J = 6.5 Hz), 7.40 (1 H, m), 7, 13 (2 H, t, J = 8.1 Hz), 4.41 (1 H, quin, J = 8.8 Hz), 4.21 (1 H, m), 4.14 (1 H, dd , J = 10.8, 9.8 Hz), 3.76 (1 H, m), 3.71 (2 H, m), 3.65 (1 H, td, J = 8.2, 5, 6 Hz), 3.45 (1 H, dd, J = 8.9, 3.7 Hz), 3.24 (2 H, s), 3.19 (1 H, dd, J = 15.6, 9.2 Hz), 2.84 (1 H, dd, J = 15.7, 8.7 Hz), 2.06 (1 H, dq, J = 12.7, 7.6 Hz), 1, 71 (1 H, m). 13

[001298] C NMR (DMSOd6): 167.5, 161.6, 161.6, 160, 159.9, 155.1, 129.8, 129.7, 129.7, 129.2, 116, 5, 116.4, 116.3, 114.2, 112.2, 112.2, 112.1, 112.1, 72.4, 66.3, 49.8, 48.6, 35.3, 32, 31.3, 29.4.

[001299] Example 78: (R) -N-cyclopropyl-2- (6- (2,3,5,6-tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) acetamide

[001300] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige powder.

[001301] 1H NMR (DMSOd6): 11.74 (1 H, s), 8.04 (1 H, br d, J = 3.7 Hz), 7.85 (1 H, m), 4, 48 (1 H, quin, J = 8.6 Hz), 4.17 (1 H, dd, J = 11.5, 9.3 Hz), 3.77 (1 H, dd, J = 11.7 , 7.9 Hz), 3.25 (1 H, dd, J = 15.8, 9.4 Hz), 3.19 (2 H, m), 2.88 (1 H, dd, J = 15 , 9, 8.2 Hz), 2.59 (1 H, tq, J = 7.4, 3.8 Hz), 0.60 (2 H, m), 0.38 (2 H, m). 13

[001302] C NMR (DMSOd6): 168.7, 155.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144, 6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.3, 105.9, 105.7, 105.5, 48.4, 35.7, 31.3, 29.2, 22.4, 5.6, 5.6.

[001303] Example 79: (R) -N- (cyclopropylmethyl) -2- (6- (2,3,5,6- tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazol-1-yl) acetamide

[001304] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[001305] 1H NMR (DMSOd6): 11.76 (1 H, s), 8.05 (1 H, br t, J = 5.4 Hz), 7.85 (1 H, m), 4, 48 (1 H, quin, J = 8.6 Hz), 4.17 (1 H, dd, J = 11.6, 9.1

Hz), 3.77 (1 H, dd, J = 11.6, 7.9 Hz), 3.25 (1 H, dd, J = 9.3, 11.7 Hz), 3.24 (2 H, s), 2.92 (2 H, t, J = 6.2 Hz), 2.89 (1 H, dd, J = 16.1, 8.3 Hz), 0.87 (1 H, m), 0.38 (2 H, m), 0.13 (2 H, m). 13

[001306] C NMR (DMSOd6): 167.4, 155.2, 146.4, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144, 7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.4, 105.9, 105.7, 105.6, 48.4, 43.1, 35.8, 31.5, 29.2, 10.7, 3.2.

[001307] Example 80: (R) -N-cyclobutyl-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) acetamide

[001308] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige powder.

[001309] 1H NMR (DMSOd6): 11.74 (1 H, s), 8.20 (1 H, br d, J = 7.6 Hz), 7.85 (1 H, m), 4, 48 (1 H, quin, J = 8.5 Hz), 4.16 (2 H, m), 3.77 (1 H, dd, J = 11.6, 7.9 Hz), 3.24 ( 1 H, br dd, J = 15.8, 9.2 Hz), 3.20 (2 H, s), 2.87 (1 H, br dd, J = 15.8, 8.1 Hz), 2.12 (2 H, m), 1.86 (2 H, m), 1.60 (2 H, m). 13

[001310] C NMR (DMSOd6): 166.5, 155.2, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143, 7, 143.7, 143.6,

143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.3, 105.9, 105.7, 105.5, 48.4, 44, 35.7, 31.4, 30.2, 30.2, 29.2, 14.6.

[001311] Example 81: (R) -1- (4-methylpiperazin-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[001312] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[001313] 1H NMR (DMSOd6): 11.70 (1 H, br s), 7.85 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4, 18 (1 H, dd, J = 11.4, 9.3 Hz), 3.78 (1 H, dd, J = 11.7, 7.7 Hz), 3.50 (2H, m), 3 , 48-3.38 (4H, m), 3.24 (1 H, br dd, J = 15.8, 9.4 Hz), 2.85 (1 H, dd, J = 15.8, 7 , 9 Hz), 2.26 (4 H, m), 2.17 (3 H, s). 13

[001314] C NMR (DMSOd6): 166.5, 155.2, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 143, 6, 143.6, 143.5, 129, 120.5, 120.4, 120.3, 114.2, 105.8, 105.7, 105.5, 54.6, 54.2, 48, 5, 45.6, 45.1, 41.2, 35.8, 29.2, 29.1.

[001315] Example 82: (R) -1- (4-hydroxypiperidin-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[001316] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[001317] 1H NMR (DMSOd6): 11.70 (1 H, br s), 7.85 (1 H, m), 4.75 (1 H, s br), 4.48 (1 H, quin , J = 8.5 Hz), 4.18 (1 H, m), 3.86 (1 H, m), 3.77 (1 H, dd, J = 11.6, 7.9 Hz), 3.67 (2 H, m), 3.49 (2 H, m), 3.24 (1 H, br dd, J = 15.8, 9.2 Hz), 3.16 (1 H, m ), 3.01 (1 H, m), 2.86 (1 H, dd, J = 15.8, 7.9 Hz), 1.69 (2 H, m), 1.32 (1 H, br d, J = 9.1 Hz), 1.24 (1 H, m). 13

[001318] C NMR (DMSOd6): 66.2, 155.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143, 7, 143.7, 143.6, 143.6, 143.6, 143.6, 129, 120.5, 120.4, 120.2, 114.4, 105.9, 105.7, 105, 5, 65.4, 65.4, 48.4, 42.8, 39, 35.8, 34.5, 34.4, 33.8, 29.2, 29.1, 29.1.

[001319] Example 83: (R) -1- (4- (hydroxymethyl) piperidin-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[001320] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige powder.

[001321] 1H NMR (DMSOd6): 11.71 (1 H, br d, J = 5.1 Hz), 7.85 (1 H, m), 4.48 (1 H, m), 4, 48 (1H, br), 4.34 (1 H, br d, J = 11.6 Hz), 4.17 (1 H, m), 3.84 (1 H, br d, J = 12.5 Hz), 3.77 (1 H, m), 3.48 (2 H, m), 3.23 (3 H, m), 2.98 (1 H, m), 2.86 (1 H, m), 2.52 (1 H, m), 1.74-1.51 (3 H, m), 0.98 (2 H, m). 13

[001322] C NMR (DMSOd6): 166.1, 166.1, 155.2, 155.1, 146.4, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145, 2, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.5, 128.9, 120.4, 120.3, 120.2, 114.5, 114.4, 105.9, 105.7, 105.5, 65.5, 65, 5, 48.5, 45.3, 45.3, 41.3, 38.3, 38.3, 35.8, 35.7, 29.2, 29.2, 29, 28.3, 28, 3.

[001323] Example 84: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-cyclopentylacetamide

[001324] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a white solid.

[001325] 1H NMR (DMSOd6): 11.55 (1 H, br s), 7.93 (1 H, br d,

J = 7.2 Hz), 7.61 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 9.6, 10.5 Hz), 3.96 (1 H, sxt, J = 6.8 Hz), 3.73 (1 H, dd, J = 11.5, 8, 0 Hz), 3.21 (1 H, m), 3.20 (2 H, s), 2.83 (1 H, br dd, J = 15.8, 8.1 Hz), 1.76 ( 2 H, m), 1.61 (2 H, m), 1.48 (2 H, m), 1.35 (2 H, m). 13

[001326] C NMR (DMSOd6): 166.9, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 128.9, 118.8, 118.7, 118.6, 116, 115.9, 114.5, 113.2, 113.2, 113.1, 113.1, 50.5, 48.5, 35.6, 32.2, 32.2, 31.5, 29.3, 23.4.

[001327] Example 85: (R) -N, N-dimethyl-2- (4- (2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) piperazin-1-yl) acetamide

[001328] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light beige powder.

[001329] 1H NMR (DMSOd6): 11.71 (1 H, m), 7.85 (1 H, m), 4.50 (1 H, quin, J = 8.5 Hz), 4.18 (1 H, dd, J = 11.2, 9.5 Hz), 3.77 (1 H, dd, J = 11.6, 7.8 Hz), 3.50 (2 H, s), 3 , 44 (4 H, m), 3.24 (1 H, br dd, J = 15.8, 9.5 Hz), 3.16 (2 H, s), 2.99 (3 H, s) , 2.86 (1 H, dd, J = 7.8, 15.7 Hz), 2.80 (3 H, s), 2.41 (4 H, m). 13

[001330] C NMR (DMSOd6): 168.7, 166.4, 155.2, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144, 7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 129,

120.5, 120.4, 120.3, 114.2, 105.8, 105.7, 105.5, 59.5, 52.5, 52.1, 48.5, 45.2, 41, 3, 36.6, 35.8, 34.9, 29.2, 29.

[001331] Example 86: (R) -1- (2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [ 1,2-c] imidazol-1-yl) acetyl) piperidine-4-carboxamide

[001332] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige powder.

[001333] 1H NMR (DMSOd6): 11.70 (1 H, br d, J = 4.5 Hz), 7.85 (1 H, quin, J = 8.7 Hz), 7.28 (1 H, br s, 6.80 (1 H, br s), 4.49 (1 H, quin, J = 8.4 Hz), 4.30 (1 H, br d, J = 13.1 Hz ), 4.18 (1 H, dd, J = 9.7, 11.3 Hz), 3.86 (1 H, br d, J = 11.9 Hz), 3.77 (1 H, dd, J = 11.7, 7.8 Hz), 3.50 (2 H, m), 3.24 (1 H, ddd, J = 15.7, 9.1, 6.5 Hz), 3.02 (1 H, m), 2.87 (1 H, dd, J = 7.9, 15.7 Hz), 2.60 (1 H, m), 2.32 (1 H, tt, J = 11 , 4, 3.8 Hz), 1.69 (2 H, m), 1.47 (1 H, m), 1.35 (1 H, m). 13

[001334] C NMR (DMSOd6): 175.9, 175.9, 166.3, 166.2, 155.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144, 7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 143.6, 129, 120.4, 120.3, 120.2, 114.4, 105.9, 105.7, 105.5, 48.4, 44.8, 41.2, 41, 35.8, 29.1, 29.1, 29, 28.7, 28.1.

[001335] Example 87: (R) -1- (1,4-dioxa-8-azospiro [4.5] decan-8-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -thioxy-2,5,6,7-tetrahydro-3H-pyrrole [1,2-

c] imidazol-1-yl) ethan-1-one

[001336] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a white powder.

[001337] 1H NMR (DMSOd6): 11.68 (1 H, m), 7.85 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.4, 9.2 Hz), 3.90 (4 H, s), 3.78 (1 H, dd, J = 11.7, 7.7 Hz), 3 , 53 (2 H, s), 3.49 (4 H, m), 3.24 (1 H, dd, J = 15.8, 9.4 Hz), 2.85 (1 H, dd, J = 15.8, 7.9 Hz), 1.63 (2 H, m), 1.55 (2 H, br s). 13

[001338] C NMR (DMSOd6): 166.4, 155.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143, 6, 143.6, 143.6, 143.6, 143.6, 129.1, 120.5, 120.4, 120.3, 114.3, 106.3, 105.8, 105.7, 105.5, 63.8, 48.4, 43.4, 35.8, 34.9, 34.3, 29.2, 29.

[001339] Example 88: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-isopropylacetamide

[001340] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a white solid.

[001341] 1H NMR (DMSOd6): 11.75 (1 H, br s), 7.86 (1 H, br d, J = 7.5 Hz), 7.61 (1 H, m), 7 , 22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.3 Hz), 3.80 (1 H, m), 3.72 (1 H, dd, J = 11.6, 8.1 Hz), 3.21 (1 H, dd, J = 9.2, 15.8 Hz), 3 , 19 (2 H, s), 2.84 (1 H, dd, J = 15.8, 8.3 Hz), 1.03 (6 H, d, J = 6.6 Hz). 13

[001342] C NMR (DMSOd6): 166.5, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 128.9, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114.5, 113.2, 113.2, 113.1, 113.1, 48.5, 40.6, 35.6, 31.5, 29.3, 22.3.

[001343] Example 89: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (3-morpholinopropyl) acetamide

[001344] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a white solid.

[001345] 1H NMR (DMSOd6): 11.75 (1 H, s), 7.93 (1 H, br t, J = 5.5 Hz), 7.62 (1 H, m), 7, 22 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 11.2, 9.4 Hz), 3.73 ( 1 H, dd, J = 11.5, 8.1 Hz), 3.53 (4 H, br t, J = 4.5 Hz), 3.22 (2 H, s), 3.21 (1 H, m), 3.06 (2 H, m), 2.84 (1 H, dd, J = 15.8, 8.4 Hz), 2.29 (4 H, br s), 2.24 (2 H, br t, J = 7.2 Hz), 1.53 (2 H, quin, J = 7.1 Hz). 13

[001346] C NMR (DMSOd6): 167.5, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 154.9, 154.9, 129.7, 129.7, 129, 118.7, 118.6, 118.5, 116.1, 116.1, 116, 115.9, 114.3, 113.3, 113.2, 113, 1, 113.1, 66.2, 55.8, 53.3, 48.5, 37.1, 35.6, 31.5, 29.3, 25.9.

[001347] Example 90: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[001348] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[001349] 1H NMR (DMSOd6): 11.75 (1 H, s), 8.22 (1 H, d, J = 6.6

Hz), 7.72 (1 H, td, J = 8.4, 5.7 Hz), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz) , 4.20 (1 H, m), 4.14 (1 H, dd, J = 11.4, 9.2 Hz), 3.76 (1 H, m), 3.72 (2 H, m ), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 8.9, 3.6 Hz), 3.24 (2 H , s), 3.21 (1 H, dd, J = 9.3, 15.7 Hz), 2.83 (1 H, dd, J = 15.6, 8.1 Hz), 2.06 ( 1 H, m), 1.71 (1 H, m). 13

[001350] C NMR (DMSOd6): 167.5, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.8, 118.7, 118.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 72.4, 66.3, 49.8, 48.6, 35.6, 32, 31.3, 29.3.

[001351] Example 91: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (4-methylpiperazin-1-yl) ethan-1-one

[001352] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream solid.

[001353] 1H NMR (DMSOd6): 11.70 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.15 (1 H, dd, J = 11.4, 9.4 Hz), 3.72 (1 H, dd, J = 11.7, 7.8 Hz), 3 , 49 (2 H, m), 3.43 (4 H, m), 3.20 (1 H, dd, J = 15.8, 9.3 Hz), 2.81 (1 H, dd, J = 15.8, 8.0 Hz), 2.26 (4 H, m), 2.17 (3 H, s). 13

[001354] C NMR (DMSOd6): 166.5, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.2, 118.9, 118.7, 118.6, 114.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 54.6,

54.2, 48.6, 45.6, 45.1, 41.2, 35.7, 29.3, 29.1.

[001355] Example 92: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-butyl-N-methylacetamide

[001356] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light beige solid.

[001357] 1H NMR (DMSOd6): 11.71 (1 H, br s), 7.72 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, m) , 4.15 (1 H, dd, J = 9.4, 11.3 Hz), 3.72 (1 H, dd, J = 11.5, 7.8 Hz), 3.47 (2 H, m), 3.24 (3 H, m), 2.95 (1.6 H, s), 2.82 (1 H, m), 2.79 (1.4 H, s), 1.49 (1 H, quin, J = 7.6 Hz), 1.40 (1 H, m), 1.31-1.15 (2 H, m), 0.90, 0.85 (3 H, 2 t, J = 7.2 Hz). 13

[001358] C NMR (DMSOd6): 167.6, 167.5, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155, 132.5, 132.4, 129.2, 129.1, 118.8, 118.8, 118.7, 118.7, 118.6, 118.6, 114.4, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 49.1, 48.6, 46.7, 35.7, 35, 33, 1, 30, 29.4, 29.3, 29.3, 28.9, 28.8, 19.5, 19.3, 13.7.

[001359] Example 93: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-hydroxyethyl) acetamide

The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light beige powder.

[001361] 1H NMR (DMSOd6): 11.73 (1 H, s), 7.96 (1 H, br t, J = 5.5 Hz), 7.72 (1 H, m), 7, 17 (1 H, m), 4.67 (1 H, br s), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 9.5 , 11.4 Hz), 3.72 (1 H, dd, J = 11.5, 8.1 Hz), 3.39 (2 H, br t, J = 5.7 Hz), 3.24 ( 2 H, m), 3.21 (1 H, dd, J = 15.7, 9.5 Hz), 3.11 (2 H, q, J = 6.0 Hz), 2.84 (1 H , dd, J = 15.8, 8.4 Hz). 13

[001362] C NMR (DMSOd6): 167.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.7, 118.6, 118.4, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 59.7, 48.5, 41.7, 35.7, 31.5, 29.2.

[001363] Example 94: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-cyclopropylacetamide

[001364] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a brown powder.

[001365] 1H NMR (DMSOd6): 11.73 (1 H, s), 8.03 (1 H, br d, J = 3.5 Hz), 7.72 (1 H, td, J = 8 , 4, 5.9 Hz), 7.16 (1 H, t, J = 9.5 Hz), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 9.6, 11.2 Hz), 3.72 (1 H, dd, J = 11.4, 8.1 Hz), 3.21 (1 H, dd, J = 9.7, 15.9 Hz), 3.18 (2 H, s), 2.83 (1 H, dd, J = 15.6, 8.3 Hz), 2.59 (1 H, m), 0.59 (2 H, m), 0.38 (2 H, m). 13

[001366] C NMR (DMSOd6): 168.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.7, 118.6, 118.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.5, 35.6, 31.3, 29.3, 22.4, 5.6, 5.6.

[001367] Example 95: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (cyclopropylmethyl) acetamide

[001368] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[001369] 1H NMR (DMSOd6): 11.75 (1 H, s), 8.04 (1 H, t, J = 5.5 Hz), 7.72 (1 H, ddd, J = 8, 9, 8.1, 5.8 Hz), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 11.4, 9.3 Hz), 3.72 (1 H, dd, J = 11.6, 8.1 Hz), 3.24 (2 H, s), 3.22 (1 H, dd, J = 9.5, 15.7 Hz), 2.92 (2 H, t, J = 6.2

Hz), 2.84 (1 H, dd, J = 15.7, 8.2 Hz), 0.87 (1 H, m), 0.37 (2 H, m), 0.13 (2 H , m). 13

[001370] C NMR (DMSOd6): 167.4, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.7, 118.6, 118.5, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.5, 43.1, 35.6, 31.5, 29.3, 10.7, 3.2.

[001371] Example 96: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) acetamide

[001372] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light beige powder.

[001373] 1H NMR (DMSOd6): 11.73 (1 H, s), 7.72 (1 H, td, J = 8.4, 5.7 Hz), 7.37 (1 H, br s ), 7.17 (1 H, m), 7.02 (1 H, br s), 4.45 (1 H, quin, J = 8.8 Hz), 4.14 (1 H, dd, J = 9.5, 11.2 Hz), 3.73 (1 H, dd, J = 11.5, 8.1 Hz), 3.23 (1 H, dd, J = 9.3, 16.0 Hz), 3.21 (2 H, d, J = 4.8 Hz), 2.85 (1 H, dd, J = 15.7, 8.4 Hz). 13

[001374] C NMR (DMSOd6): 169.8, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.2, 118.7, 118.5, 118.4, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.5, 35.7, 31.2, 29.2.

[001375] Example 97: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-propylacetamide

[001376] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[001377] 1H NMR (DMSOd6): 11.74 (1 H, s), 7.91 (1 H, br t, J = 5.5 Hz), 7.72 (1 H, ddd, J = 8 , 8, 8.1, 5.8 Hz), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 11.4, 9.3 Hz), 3.72 (1 H, dd, J = 11.5, 8.0 Hz), 3.23 (2 H, s), 3.20 (1 H, dd , J = 9.0, 15.8 Hz), 2.99 (2 H, m), 2.83 (1 H, dd, J = 15.8, 8.3 Hz), 1.39 (2 H , sxt, J = 7.2 Hz), 0.82 (3 H, t, J = 7.4 Hz). 13

[001378] C NMR (DMSOd6): 167.4, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.2, 129.1, 118.7, 118.6, 118.5, 114.3, 113.8, 113.8, 113.6, 113.6, 104, 1, 104, 103.9, 103.9, 48.5, 40.5, 35.7, 31.5, 29.3, 22.3, 11.4.

[001379] Example 98: 1 - ((S) -2- (hydroxymethyl) pyrrolidin-1-yl) -2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo- 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[001380] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light beige powder.

[001381] 1H NMR (DMSOd6): 11.72 (1 H, br s), 7.85 (1 H, m), 5.18- 4.57 (1 H, 2 br s), 4.48 (1 H, quin, J = 8.5 Hz), 4.18 (1 H, br t, J = 10.3 Hz), 4.0-3.86 (1 H, 2 m), 3.78 (1 H, br dd, J = 11.5, 7.8 Hz), 3.67-3.18 (7 H, multiplets), 2.87 (1 H, br dd, J = 15.7, 7 , 9 Hz), 2.01-1.68 (4 H, m). 13

[001382] C NMR (DMSOd6): 166.8, 166.7, 155.1, 155, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146, 2, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 129, 129, 120.5, 120.4, 120.3, 114.6, 114.1, 105.8, 105, 7, 105.5, 62.6, 60.9, 58.8, 58.8, 48.4, 47, 45.5, 35.8, 35.7, 30.7, 30, 29.2, 27.8, 26.7, 23.4, 21.4.

[001383] Example 99: (S) -N-cyclobutyl-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) acetamide

[001384] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige powder.

[001385] 1H NMR (DMSOd6): 11.74 (1 H, s), 8.20 (1 H, br d, J = 7.6 Hz), 7.85 (1 H, m), 4, 48 (1 H, quin, J = 8.6 Hz), 4.16 (2 H, m), 3.77 (1 H, dd, J = 11.7, 7.8 Hz), 3.24 ( 1 H, dd, J = 15.8, 9.4 Hz), 3.20 (2 H, s), 2.87 (1 H, dd, J = 15.8, 8.1 Hz), 2, 12 (2 H, m), 1.86 (2 H, m), 1.60 (2 H, m). 13

[001386] C NMR (DMSOd6): 166.5, 155.2, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143, 6, 143.6, 143.6, 128.9, 120.3, 114.3, 105.9, 105.7, 105.6, 48.4, 44, 35.7, 31.4, 30, 2, 30.2, 29.2, 14.6.

[001387] Example 100: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1 - ((S) -2- (hydroxymethyl) pyrrolidin-1-yl) ethan-1-one

[001388] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a brown solid.

[001389] 1H NMR (DMSOd6): 11.70 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.97 (0.35 H, br s), 4.71 (0.65 H, br s), 4.45 (1 H, m), 4.15 (1 H, dd, J = 9.0, 11.2 Hz), 3.95 (0.35 H, m), 3.91 (0.65 H, m), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.57 (0.35 H , m), 3.52-3.36 (3.65 H, m), 3.31 - 3.14 (3 H, m), 2.83 (1 H, m), 1.84 (4 H , m). 13

[001390] C NMR (DMSOd6): 166.8, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155, 155, 132.5, 132.4, 129.3, 129.1, 118.9, 118.8, 118.7, 118.7, 114.5, 114, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 62.7, 60.9, 58.8, 58.8, 48.6, 48.6, 47, 45.5, 35, 6, 30.7, 30.1, 29.4, 29.3, 27.8, 26.7, 23.4, 21.4.

[001391] Example 101: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (pyrrolidin-1-yl) ethan- 1-one

[001392] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light brown powder.

[001393] 1H NMR (DMSOd6): 11.71 (1 H, s), 7.72 (1 H, m), 7.17 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.4, 9.3 Hz), 3.72 (1 H, dd, J = 11.7, 7.8 Hz), 3 , 42 (2 H, m), 3.41 (2 H, s), 3.27 (2 H, t, J =

6.9 Hz), 3.21 (1 H, dd, J = 15.7, 9.4 Hz), 2.81 (1 H, dd, J = 15.7, 8.1 Hz), 1, 87 (2 H, m), 1.76 (2 H, m). 13

[001394] C NMR (DMSOd6): 166.1, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.2, 118.9, 118.8, 118.6, 114.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.6, 46.2, 45.5, 35.6, 30.5, 29.3, 25.6, 24.

[001395] Example 102: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-cyclobutylacetamide

[001396] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light beige powder.

[001397] 1H NMR (DMSOd6): 11.73 (1 H, s), 8.20 (1 H, br d, J = 7.6 Hz), 7.72 (1 H, m), 7, 17 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (2 H, m), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.20 (1 H, dd, J = 9.3, 15.5 Hz), 3.19 (2 H, s), 2.82 (1 H, dd, J = 15, 6, 8.3 Hz), 2.12 (2 H, m), 1.86 (2 H, m), 1.60 (2 H, m). 13

[001398] C NMR (DMSOd6): 166.5, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.8, 118.6, 118.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.6, 44, 35.6, 31.4, 30.2, 30.2, 29.3, 14.7.

[001399] Example 103: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-methoxyethyl) acetamide

[001400] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige powder.

[001401] 1H NMR (DMSOd6): 11.74 (1 H, s), 8.04 (1 H, br t, J = 5.4 Hz), 7.72 (1 H, m), 7, 16 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = m), 3.72 (1 H, dd, J = 11.5, 8.0 Hz), 3.32 (2 H, t, J = 5.6 Hz), 3.24 (2 H, m), 3.22-3.17 (3 H, m) , 3.20 (3 H, s), 2.83 (1 H, dd, J = 15.8, 8.3 Hz). 13

[001402] C NMR (DMSOd6): 167.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.7, 118.6, 118.5, 114.3, 113.8, 113.8, 113.6, 104.1, 104, 103.9, 103.9, 70.5, 57.8, 48.5, 38.6, 35.6, 31.5, 29.3.

[001403] Example 104: (R) -1- (pyrrolidin-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[001404] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light beige powder.

[001405] 1H NMR (DMSOd6): 11.71 (1 H, br s), 7.85 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4, 18 (1 H, dd, J = 11.6, 9.1 Hz), 3.78 (1 H, dd, J = 11.7, 7.7 Hz), 3.42 (4 H, m), 3.27 (2 H, t, J = 7 Hz), 3.25 (1 H, dd, J = 9.3, 15.8 Hz), 2.87 (1 H, dd, J = 15.8 , 7.9 Hz), 1.88 (2 H, m), 1.76 (2 H, m). 13

[001406] C NMR (DMSOd6): 166.1, 155.1, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144, 6, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 129, 120.5, 120.4, 120.3, 114.2, 105.8, 105, 7, 105.5, 48.5, 46.1, 45.5, 35.7, 30.4, 29.2, 25.6, 24.

[001407] Example 105: (S) -1- (pyrrolidin-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[001408] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light beige powder.

[001409] 1H NMR (DMSOd6): 11.72 (1 H, br s), 7.85 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4, 18 (1 H, dd, J = 11.5, 9.2 Hz), 3.77 (1 H, dd, J = 11.6, 7.8 Hz), 3.42 (4 H, m), 3.27 (2 H, t, J = 7 Hz), 3.25 (1 H, dd, J = 9.3, 15.8 Hz), 2.87 (1 H, dd, J = 15.8 , 7.9 Hz), 1.87 (2 H, m), 1.76 (2 H,

m). 13

[001410] C NMR (DMSOd6): 166.1, 155.1, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144, 6, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 129, 120.5, 120.4, 120.3, 114, 2, 105.8, 105.7, 105.5, 48.5, 46.1, 45.5, 35.7, 30.4, 29.2, 25.6, 24.

[001411] Example 106: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole hydrochloride [1 , 2-c] imidazol-1-yl) - N- (2- (pyridin-2-yl) ethyl) acetamide

[001412] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001413] 1H NMR (DMSOd6): 11.72 (1 H, br s), 8.70 (1 H, br d, J = 5.1 Hz), 8.25 (1 H, br s), 8.12 (1 H, br t, J = 5.6 Hz), 7.71 (2 H, m), 7.62 (1 H, m), 7.23 (1 H, m), 4, 41 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 9.4, 11.4 Hz), 3.73 (1 H, dd, J = 11.4 , 8.2 Hz), 3.47 (2 H, m), 3.21 (2 H, m), 3.15 (1 H, dd, J = 15.8, 9.2 Hz), 3, 07 (2 H, t, J = 6.6 Hz), 2.79 (1 H, dd, J = 15.8, 8.4 Hz). 13

[001414] C NMR (DMSOd6): 168, 160.2, 160.1, 158.6, 158.5, 156.6, 156.6, 155.9, 155.8, 155.2, 155, 2, 155, 154.9, 143.7, 143.2, 129.8, 129.7, 129.4, 126.3, 123.9, 118.7, 118.5, 118.4, 116, 1, 116,

114.1, 114, 113.3, 113.1, 48.5, 38.1, 35.6, 34.3, 31.5, 29.2.

[001415] Example 107: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-methoxyethyl) acetamide

[001416] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001417] 1H NMR (DMSOd6): 11.74 (1 H, s), 8.04 (1 H, br t, J = 5.6 Hz), 7.61 (1 H, m), 7, 22 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 3.73 ( 1 H, dd, J = 11.6, 8.1 Hz), 3.32 (2 H, t, J = 5.5 Hz), 3.26-3.15 (5 H, m), 3, 20 (3 H, s), 2.84 (1 H, dd, J = 15.8, 8.2 Hz). 13

[001418] C NMR (DMSOd6): 167.7, 155.1, 129.7, 129.6, 129.1, 118.7, 118.6, 118.5, 116.1, 116, 115, 9, 115.9, 114.2, 113.2, 113.2, 113.1, 113.1, 70.5, 57.8, 48.5, 38.6, 35.6, 31.5, 29.2.

[001419] Example 108: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) acetamide

[001420] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001421] 1H NMR (DMSOd6): 11.73 (1 H, br s), 7.62 (1 H, m), 7.37 (1 H, br s), 7.22 (1 H, m ), 7.01 (1 H, br s), 4.45 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 9.4, 11.2 Hz) , 3.74 (1 H, dd, J = 11.5, 8.1 Hz), 3.23 (1 H, dd, J = 9.3, 15.7 Hz), 3.21 (2 H, m), 2.86 (1 H, dd, J = 15.7, 8.5 Hz). 13

[001422] C NMR (DMSOd6): 169.8, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 155, 154.9, 129, 7, 129.6, 129.2, 118.7, 118.6, 118.4, 116.1, 116, 115.9, 115.9, 114.4, 113.2, 113.2, 113, 1, 113.1, 48.5, 35.6, 31.2, 29.2.

[001423] Example 109: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole hydrochloride [1 , 2-c] imidazol-1-yl) - N- (pyridin-3-ylmethyl) acetamide

[001424] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001425] 1H NMR (DMSOd6): 11.81 (1 H, s), 8.51 (1 H, t, J = 5.9 Hz), 8.48 (1 H, dd, J = 0, 6, 2.4 Hz), 8.41 (1 H, dd, J = 4.7, 1.6 Hz), 7.65 (1 H, m), 7.62 (1 H, m), 7 , 31 (1 H, ddd, J = 0.8, 4.8, 7.8 Hz), 7.22 (1 H, m), 4.42 (1 H, quin, J = 8.7 Hz) , 4.29 (2 H, m), 4.14 (1 H, dd, J = 9.4, 11.3 Hz), 3.73 (1 H, dd, J = 11.5, 8.1 Hz), 3.32 (2 H, m), 3.14 (1 H, dd, J = 15.7, 9.2 Hz), 2.76 (1 H, dd, J = 15.8, 8 , 4 Hz). 13

[001426] C NMR (DMSOd6): 167.9, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.3, 154.9, 154.9, 148.8, 148.1, 135.2, 134.7, 129.7, 129.7, 129.3, 123.3, 118.6, 118.5, 118.4, 116.1, 116, 115.9, 115.9, 114, 113.3, 113.2, 113.1, 113.1, 48.5, 39.8, 35.6, 31.4, 29.2.

[001427] Example 110: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (pyrrolidin-1-yl) ethan- 1-one

[001428] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001429] 1H NMR (DMSOd6): 11.71 (1 H, br s), 7.61 (1 H, m), 7.21 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, dd, J = 11.2, 9.5 Hz), 3.73 (1 H, dd, J = 11.6, 7.9 Hz), 3.42 (2 H, m), 3.41 (2 H, s), 3.27 (2 H, t, J = 6.9 Hz), 3.22 (1 H, dd, J = 15, 8, 9.3 Hz), 2.82 (1 H, dd, J = 15.8,

8.1 Hz), 1.87 (2 H, m), 1.76 (2 H, m). 13

[001430] C NMR (DMSOd6): 166.1, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 129.2, 118.9, 118.8, 118.6, 116.1, 116, 115.9, 115.9, 114.1, 113.2, 113.2, 113.1, 113.1, 48.6, 46.1, 45.5, 35.6, 30.4, 29.3, 25.6, 24.

[001431] Example 111: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (4,4-difluoropiperidin-1-yl) ethan-1-one

[001432] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001433] 1H NMR (DMSOd6): 11.68 (1 H, s), 7.61 (1 H, m), 7.21 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.5, 9.2 Hz), 3.74 (1 H, dd, J = 11.7, 7.8 Hz), 3 , 57 (2 H, s), 3.56 (4 H, m), 3.23 (1 H, dd, J = 15.8, 9.3 Hz), 2.83 (1 H, dd, J = 15.7, 8.1 Hz), 2.02 (2 H, m), 1.91 (2 H, m). 13

[001434] C NMR (DMSOd6): 166.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 154.9, 154.9, 129.7, 129.6, 129.4, 124.3, 122.7, 121.1, 118.9, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114, 113.2, 113.2, 113.1, 113.1, 48.6, 42.1, 42.1, 42.1, 38.5, 38.4, 38.4, 35.6, 33.9, 33.8, 33.6, 33.3, 33.2, 33, 29.2, 28.9.

[001435] Example 112: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-

2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (1,1-dioxidotetrahydro-2H-thiopyran-4-yl) acetamide

[001436] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001437] 1H NMR (DMSOd6): 11.77 (1 H, s), 8.09 (1 H, d, J = 7.6 Hz), 7.61 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 3.93 (1 H, m), 3.73 (1 H, dd, J = 11.7, 8.0 Hz), 3.27-3.17 (5 H, m), 3.08 (2 H, m), 2.85 (1 H, dd, J = 15.8, 8.2 Hz), 2.04 (2 H, m), 1.90 (2 H, m). 13

[001438] C NMR (DMSOd6): 167.1, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 154.9, 154.9, 129.7, 129.6, 129.2, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114.1, 113.3, 113.2, 113.1, 113.1, 48.5, 48.3, 43.9, 35.6, 31.4, 29.3, 29.1.

[001439] Example 113: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2,2,2-trifluoroethyl) acetamide

[001440] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001441] 1H NMR (DMSOd6): 11.79 (1 H, s), 8.64 (1 H, br t, J = 6.3 Hz), 7.61 (1 H, m), 7, 21 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.16 (1 H, dd, J = 11.2, 9.3 Hz), 3.90 ( 2 H, qd, J = 9.8, 6.5 Hz), 3.74 (1 H, dd, J = 11.5, 8.0 Hz), 3.36 (2 H, m), 3, 21 (1 H, dd, J = 15.8, 9.3 Hz), 2.84 (1 H, dd, J = 15.8, 8.3 Hz). 13

[001442] C NMR (DMSOd6): 168.6, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.3, 154.9, 154.9, 129.7, 129.7, 129.4, 127.5, 125.6, 123.8, 121.9, 118.7, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 113.5, 113.2, 113.2, 113.1, 113.1, 48.5, 35.6, 31.1, 29.2.

[001443] Example 114: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2- (methylsulfonyl) ethyl) acetamide

[001444] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001445] 1H NMR (DMSOd6): 11.74 (1 H, s), 8.20 (1 H, t, J = 5.6 Hz), 7.62 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 3.74 (1 H, dd, J = 11.7, 8.1 Hz), 3.46 (2 H, m), 3.27 (2 H, m), 3.24 (2 H, t, J = 6.9 Hz), 3.23 (1 H, m), 2.99 (3 H, s), 2.87 (1 H, dd, J = 15.8, 8.4 Hz). 13

[001446] C NMR (DMSOd6): 168.1, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.3, 154.9, 154.9, 129.7, 129.6, 129.5, 118.6, 118.5, 118.4, 116.1, 115.9, 113.8, 113.2, 113.1, 53, 48.5, 40.8, 35.6, 33, 31.3, 29.2.

[001447] Example 115: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole hydrochloride [1 , 2-c] imidazol-1-yl) - N- (2- (4,4-difluoropiperidin-1-yl) ethyl) acetamide

[001448] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001449] 1H NMR (DMSOd6): 11.75 (1 H, s), 10.88 (1 H, br s), 8.28 (1 H, br t, J = 5.3 Hz), 7 , 62 (1 H, m), 7.22 (1 H, m), 4.45 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 9.4 , 11.4 Hz), 3.75 (1 H, dd, J = 8.2, 11.5 Hz), 3.64 (2 H, br s), 3.46 (2 H, q,

J = 5.9 Hz), 3.33 (2 H, m), 3.24 (1 H, dd, J = 9.2, 15.8 Hz), 3.20 (2 H, br s), 3.15 (2 H, br s), 2.88 (1 H, dd, J = 15.8, 8.5 Hz), 2.46-2.24 (4 H, 2 br s). 13

[001450] C NMR (DMSOd6): 168.5, 160.2, 160.1, 158.5, 158.5, 156.6, 155.3, 155, 129.8, 129.7, 129, 6, 118.6, 118.5, 118.4, 116.2, 116.1, 116.1, 116, 113.8, 113.3, 113.3, 113.1, 113.1, 54, 2, 48.7, 48.5, 35.6, 33.9, 31.5, 30.4, 29.3.

[001451] Example 116: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[001452] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[001453] 1H NMR (DMSOd6): 11.74 (1 H, s), 8.22 (1 H, d, J = 6.6 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.21 (1 H, m), 4.14 (1 H, dd, J = 11.4, 9 , 2 Hz), 3.76 (1 H, m), 3.71 (2 H, m), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 ( 1 H, dd, J = 8.9, 3.7 Hz), 3.24 (2 H, s), 3.22 (1 H, dd, J = 9.4, 15.8 Hz), 2, 83 (1 H, dd, J = 15.8, 8.1 Hz), 2.06 (1 H, m), 1.71 (1 H, m). 13

[001454] C NMR (DMSOd6): 167.5, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.8, 118.7,

118.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 72.4, 66.3, 49.7, 48.6, 35.6, 32, 31.3, 29.3.

[001455] Example 117: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (4,4-difluoropiperidin-1-yl) ethan-1-one

[001456] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[001457] 1H NMR (DMSOd6): 11.68 (1 H, s), 7.72 (1 H, ddd, J = 9.0, 8.0, 5.7 Hz), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, dd, J = 11.5, 9.2 Hz), 3.73 (1 H, dd, J = 11.6, 7.8 Hz), 3.56 (6 H, m), 3.22 (1 H, dd, J = 15.8, 9.3 Hz), 2.82 (1 H, dd, J = 15.8, 8.1 Hz), 2.02 (2 H, m), 1.91 (2 H, m). 13

[001458] C NMR (DMSOd6): 166.8, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.4, 124.2, 122.6, 121, 118.8, 118.7, 118.6, 114, 113.8, 113.7, 113.6, 113, 6, 104, 104, 103.9, 103.9, 48.6, 42.1, 42.1, 42.1, 38.5, 38.4, 38.4, 35.7, 33.9, 33.8, 33.6, 33.3, 33.2, 33, 29.3, 28.9.

[001459] Example 118: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2- (methylsulfonyl) ethyl) acetamide

[001460] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light brown powder.

[001461] 1H NMR (DMSOd6): 11.74 (1 H, s), 8.19 (1 H, t, J = 5.7 Hz), 7.72 (1 H, ddd, J = 8, 9, 8.1, 5.8 Hz), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 3.73 (1 H, dd, J = 11.6, 8.2 Hz), 3.46 (2 H, m), 3.30-3.18 (5 H, m), 2.99 (3 H, s), 2.86 (1 H, dd, J = 15.8, 8.4 Hz). 13

[001462] C NMR (DMSOd6): 168.1, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.3, 132.5, 132.4, 129.5, 118.6, 118.5, 118.4, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 53, 48.5, 40.8, 35.7, 33, 31.3, 29.2.

[001463] Example 119: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-hydroxyethyl) acetamide

[001464] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[001465] 1H NMR (DMSOd6): 11.72 (1 H, s), 7.95 (1 H, t, J = 5.5 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.66 (1 H, t, J = 5.4 Hz), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 11.4, 9.3 Hz), 3.72 (1 H, dd, J = 11.6, 8.1 Hz), 3.39 (2 H, q, J = 5.9 Hz), 3.24 (2 H, m), 3.21 (1 H, dd, J = 15.8, 9.5 Hz), 3.11 (2 H, q, J = 6.0 Hz), 2, 84 (1 H, dd, J = 15.8, 8.4 Hz). 13

[001466] C NMR (DMSOd6): 167.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.7, 118.6, 118.4, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 59.7, 48.5, 41.7, 35.7, 31.5, 29.3.

[001467] Example 120: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2- (hydroxymethyl) cyclopentyl) acetamide

[001468] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light brown powder.

[001469] 1H NMR (DMSOd6): 11.76 (1 H, br s), 7.80 (0.5 H, d, J = 4.5 Hz), 7.80 (0.5 H, d , J = 4.5 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, m), 4.32 (1 H, m), 4 , 15 (1 H, dd, J = 11.1, 9.8 Hz), 4.08 (1 H, m), 3.72 (1 H, dd, J = 11.0, 8.2 Hz) , 3.33 (1 H, m), 3.27 (2 H, s), 3.25 (1 H, m), 3.24 (1 H, m), 2.84 (1 H, m) , 1.98 (1 H, m), 1.80 (1 H, m), 1.65 (2 H, m), 1.47 (2 H, m), 1.33 (1 H, m) . 13

[001470] C NMR (DMSOd6): 167.8, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129, 129, 118.8, 118.7, 118.5, 114.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 60.9, 51.5, 51.5, 48.6, 45, 45, 35.7, 35.6, 31.4, 31.3, 31.3, 29, 3, 26.2, 26.2, 21.5.

[001471] Example 121: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (3-hydroxypiperidin-1-yl) ethan-1-one

[001472] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light brown powder.

[001473] 1H NMR (DMSOd6): 11.68 (1 H, m), 7.72 (1 H, ddd, J = 8.7, 8.1, 5.8 Hz), 7.16 (1 H, m), 4.89 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, m), 4.08 (0.5 H , m), 3.72 (1 H, dd, J = 11.5, 8.0 Hz), 3.64-3.43 (4 H, m), 3.35 (0.5 H, m) , 3.26-3.13 (1.5 H, m), 3.10 (0.5 H, m), 3.00 (0.5 H, m), 2.81 (1 H, m) , 2.57 (0.5 H, m), 1.87-

1.72 (1 H, 2 m), 1.65 (1 H, m), 1.44 (0.5 H, m), 1.31 (1.5 H, m). 13

[001474] C NMR (DMSOd6): 166.7, 166.7, 166.4, 166.4, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 132.5, 132.4, 129.1, 118.9, 118.8, 118.7, 118.6, 118.6, 118.5, 114, 4, 114.3, 114.3, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 65, 64.9, 54.9, 52.3, 48.6, 45.4, 45.4, 41.7, 41.7, 35.7, 32.8, 32.8, 32.3, 32.3, 29, 3, 29.2, 29.1, 29, 23.4, 23.4, 21.7, 21.7.

[001475] Example 122: (R) -2 - ((2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) acetamido) methyl) tert-butyl pyrrolidine-1-carboxylate

[001476] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light brown powder.

[001477] 1H NMR (DMSOd6): 11.74 (1 H, 2 s), 8.00 (1 H, m), 7.72 (1 H, td, J = 8.4, 5.8 Hz ), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 9.5, 11.4 Hz), 3.72 (1 H, dd, J = 8.0, 11.5 Hz), 3.71 (1 H, m), 3.25 (2 H, s), 3.20 (3 H, m) , 3.07, 2.96 (1 H, 2 m), 2.83 (1 H, m), 1.87-1.58 (5 H, m), 1.38 (9 H, s). 13

[001478] C NMR (DMSOd6): 167.8, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.2, 153.9, 153.4, 132.5, 132.4, 129.2,

129, 118.7, 118.6, 118.5, 118.5, 114.3, 114.3, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 78.4, 56.4, 48.5, 46.4, 46.1, 40.9, 35.7, 31.5, 29.3, 28.1, 27.6, 23.1, 22.2.

[001479] Example 123: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (4- (methylsulfonyl) piperidin-1-yl) ethan-1-one

[001480] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige solid.

[001481] 1H NMR (DMSOd6): 11.69 (1 H, 2 s), 7.72 (1 H, m), 7.16 (1 H, m), 4.48 (1 H, m) , 4.44 (1 H, quin, J = 8.5 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 4.01 (1 H, br d, J = 13.6 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.54 (2 H, m), 3.36 (1 H, m), 3, 21 (1 H, m), 3.07 (1 H, m), 2.94 (3 H, s), 2.82 (1 H, m), 2.61 (1 H, m), 2, 04 (2 H, br d, J = 12.5 Hz), 1.56 (1 H, m), 1.42 (1 H, m). 13

[001482] C NMR (DMSOd6): 166.5, 166.5, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.3, 129.2, 118.7, 118.6, 118.5, 114.2, 113.8, 113.8, 113.6, 113, 6, 104, 104, 103.9, 103.9, 58.4, 58.4, 48.6, 43.9, 37.5, 35.7, 29.2, 29, 29, 24.7, 24.1.

[001483] Example 124: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (pyridin-3-ylmethyl) acetamide

[001484] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a bronze solid.

[001485] 1H NMR (DMSOd6): 11.80 (1 H, br s), 8.51 (1 H, t, J = 5.6 Hz), 8.48 (1 H, s), 8, 41 (1 H, d, J = 3.7 Hz), 7.73 (1 H, m), 7.65 (1 H, d, J = 7.8 Hz), 7.31 (1 H, dd , J = 7.6, 4.8 Hz), 7.17 (1 H, t, J = 9.3 Hz), 4.42 (1 H, quin, J = 8.7 Hz), 4.29 (2 H, d, J = 5.7 Hz), 4.14 (1 H, t, J = 10.3 Hz), 3.72 (1 H, dd, J = 11.3, 8.4 Hz ), 3.33 (2 H, m), 3.13 (1 H, br dd, J = 15.7, 9.2 Hz), 2.75 (1 H, br dd, J = 15.7, 8.4 Hz). 13

[001486] C NMR (DMSOd6): 167.9, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.3, 148.8, 148.1, 135.1, 134.7, 132.5, 132.4, 129.3, 123.3, 118.6, 118.5, 118.3, 114, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.5, 39.8, 35.6, 31.4, 29.2.

[001487] Example 125: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (1,1-dioxidothiomorpholine) ethan-1-one

[001488] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[001489] 1H NMR (DMSOd6): 11.63 (1 H, s), 7.72 (1 H, ddd, J = 8.7, 8.1, 5.8 Hz), 7.17 (1 H, m), 4.46 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.3, 9.4 Hz), 3.87 (4 H, m), 3.73 (1 H, dd, J = 11.6, 7.9 Hz), 3.62 (2 H, s), 3.26 (2 H, br m), 3.23 (1 H, dd, J = 15.9, 9.3 Hz), 3.10 (2 H, br t, J = 4.9 Hz), 2.84 (1 H, dd, J = 15.8, 8 , 1 Hz). 13

[001490] C NMR (DMSOd6): 167.4, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.5, 118.8, 118.7, 118.6, 113.8, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 51.3, 51.1, 48.6, 43.8, 40.3, 35.7, 29.2, 28.7.

[001491] Example 126: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (4- (methylsulfonyl) piperidin-1-yl) ethan-1-one

[001492] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[001493] 1H NMR (DMSOd6): 11.69 (1 H, 2 s), 7.72 (1 H, m), 7.16 (1 H, m), 4.48 (1 H, m) , 4.44 (1 H, quin, J = 8.5 Hz), 4.15 (1 H, dd, J =

11.4, 9.2 Hz), 4.01 (1 H, br d, J = 13.6 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3 , 54 (2 H, m), 3.36 (1 H, m), 3.21 (1 H, m), 3.07 (1 H, m), 2.94 (3 H, s), 2 , 82 (1 H, m), 2.61 (1 H, m), 2.04 (2 H, br d, J = 12.5 Hz), 1.56 (1 H, m), 1.42 (1 H, m). 13

[001494] C NMR (DMSOd6): 166.5, 166.5, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.3, 129.2, 118.7, 118.6, 118.5, 114.2, 113.8, 113.8, 113.6, 113, 6, 104, 104, 103.9, 103.9, 58.4, 58.4, 48.6, 43.9, 37.5, 35.7, 29.2, 29, 29, 24.7, 24.1.

[001495] Example 127: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -1-cyclohexylethyl) acetamide

[001496] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[001497] 1H NMR (DMSOd6): 11.76 (1 H, s), 7.73 (2 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.2 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3 , 57 (1 H, m), 3.22 (3 H, m), 2.81 (1 H, dd, J = 15.7, 8.2 Hz), 1.64 (4.7 H, m ), 1.23 (1.3 H, m), 1.09 (3 H, m), 0.97 (3 H, d, J = 6.7 Hz), 0.88 (2 H, m) . 13

[001498] C NMR (DMSOd6): 166.7, 160.8, 160.7, 159.1, 159.1, 157.6, 157.5, 155.9, 155.9, 155, 132, 5, 132.4, 128.8, 118.8, 118.7, 118.6, 114.6, 113.8, 113.7, 113.6, 113.6, 104.1, 104, 103, 9, 103.9, 48.7,

48.5, 42.3, 35.6, 31.6, 29.5, 28.8, 28.5, 26, 25.7, 25.7, 17.5.

[001499] Example 128: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[001500] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a green powder.

[001501] 1H NMR (DMSOd6): 11.69 (1 H, br s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1.6 H, m), 4.15 (1 H, m), 3.88 (2.4 H, m), 3.73 (1 H, br dd, J = 11.5, 7.8 Hz), 3.57 , 3.48 (2 H, 2 m), 3.40 (1 H, m), 3.34 (1 H, m), 3.21 (1 H, m), 2.84, 2.71 ( 3 H, 2 s), 2.80 (1 H, dd, J = 7.4, 15.3 Hz), 1.82-1.61 (2 H, m), 1.52 (1 H, m ), 1.38 (1 H, m). 13

[001502] C NMR (DMSOd6): 167.6, 167.6, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 155, 132.4, 132.4, 129.3, 129.2, 118.9, 118.8, 118.7, 114.4, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 66.5, 66.5, 66.2, 49.6, 48.6, 35.7, 30.2, 30.2, 30, 29.5, 29.4, 29.3, 29.2, 27.

[001503] Example 129: (R) -N- (1,1-dioxidotetrahydro-2H-thiopyran-4-yl) - 2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxus -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[001504] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[001505] 1H NMR (DMSOd6): 11.78 (1 H, s), 8.10 (1 H, d, J = 7.6 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.6 Hz), 4.17 (1 H, dd, J = 11.4, 9.2 Hz), 3.93 (1 H, m), 3.77 (1 H, dd, J = 11.6, 7.8 Hz), 3.28 - 3.17 (3 H, m), 3.26 (2 H, s), 3.08 (2 H, m), 2.89 (1 H, dd, J = 8.0, 15.8 Hz), 2.04 (2 H, br d, J = 11.3 Hz), 1.90 (2 H, m). 13

[001506] C NMR (DMSOd6): 167.1, 155.2, 146.4, 146.3, 146.2, 145.3, 145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 129, 120.4, 120.3, 120.2, 114.2, 105.9, 105.7, 105.6, 48.4, 48.3, 43.9, 35.7, 31.4, 29.2, 29.1.

[001507] Example 130: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (1,1-dioxidotetrahydro-2H-thiopyran-4-yl) acetamide

[001508] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[001509] 1H NMR (DMSOd6): 11.77 (1 H, s), 8.09 (1 H, d, J = 7.6 Hz), 7.72 (1 H, ddd, J = 8, 8, 8.2, 5.9 Hz), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.2, 9.5 Hz), 3.93 (1 H, m), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.24 (2 H, s) , 3.22 (3 H, m), 3.08 (2 H, m), 2.84 (1 H, dd, J = 15.7, 8.1 Hz), 2.04 (2 H, m ), 1.90 (2 H, m). 13

[001510] C NMR (DMSOd6): 167.1, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 132.5, 132.4, 129.2, 118.8, 118.7, 118.5, 114.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.6, 48.3, 43.9, 35.6, 31.4, 29.3, 29.1.

[001511] Example 131: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (2-hydroxyethyl) -N- methylacetamide

[001512] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a pale brown powder.

[001513] 1H NMR (DMSOd6): 11.69 (1 H, 2 s), 7.72 (1 H, ddd, J = 8.6, 8.1, 5.9 Hz), 7.16 ( 1 H, m), 4.87 (0.6 H, t, J = 5.4 Hz), 4.64 (0.4 H, t, J = 5.4 Hz), 4.44 (1 H , 2 quin, J = 8.7 Hz), 4.15 (1 H, m), 3.72 (1 H, dd, J = 11.5, 8.0 Hz), 3.54 (2 H, m), 3.46 (2 H, m), 3.40-3.29 (2 H, m), 3.20 (1 H, m), 3.02 (1.2 H, s), 2 , 82 (1.8 H, s), 2.81 (1 H, m). 13

[001514] C NMR (DMSOd6): 168.2, 167.9, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155, 132.5, 132.4, 129.2, 129.1, 118.8, 118.8, 118.7, 118.6, 118.6, 118.5, 114.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104, 104, 103.9, 103.9, 58.5, 58.4, 51.6, 50, 48.6, 36.4, 35.6, 33.4, 29.4, 29.3, 29.2, 29.1, 29.

[001515] Example 132: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-cyclohexyl-N-methylacetamide

[001516] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a brown powder.

[001517] 1H NMR (DMSOd6): 11.69 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.4 Hz), 4.20 (0.6 H, tt, J = 3.8, 11.8 Hz), 4.15 (1 H, m), 3.72 (1 H, br dd, J = 11.5, 7.7 Hz), 3.58 (0.4 H, tt, J = 11.6, 3.5

Hz), 3.51 (0.8 H, m), 3.46 (1.2 H, m), 3.21 (1 H, br dd, J = 15.8, 9.3 Hz), 2 , 80 (1 H, m), 2.81, 2.69 (3 H, 2 s), 1.84-0.97 (10 H, m). 13

[001518] C NMR (DMSOd6): 167.3, 167.3, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155, 155, 132.4, 132.4, 129.2, 129.1, 118.9, 118.8, 118.8, 114.5, 114.3, 113.8, 113.7, 113, 6, 113.6, 104.1, 104, 103.9, 103.9, 55.7, 52, 48.6, 35.7, 30.2, 30.2, 30, 29.4, 29, 4, 29.3, 29.2, 29.2, 29.2, 26.9, 25.3, 25.1, 25.1, 25, 24.8.

[001519] Example 133: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-isopropylacetamide

[001520] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[001521] 1H NMR (DMSOd6): 11.74 (1 H, s), 7.84 (1 H, br d, J = 7.5 Hz), 7.72 (1 H, ddd, J = 5 , 8, 8.1, 8.8 Hz), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.2 Hz), 3.80 (1 H, hep, J = 6.7 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3 , 21 (1 H, dd, J = 9.2, 15.8 Hz), 3.19 (2 H, s), 2.83 (1 H, dd, J = 15.7, 8.2 Hz) , 1.04 (6 H, d, J = 6.6 Hz). 13

[001522] C NMR (DMSOd6): 166.5, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155, 132, 5, 132.4, 129, 118.8, 118.7, 118.5, 114.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.6, 40.6, 35.6, 31.5, 29.4, 22.3.

[001523] Example 134: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-

2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N-methyl-N- (pyridin-3-ylmethyl) acetamide

[001524] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige solid.

[001525] 1H NMR (DMSOd6): 11.76, 1.75 (1 H, 2 br s), 8.52 (0.7 H, m), 8.49 (0.7 H, d, J = 1.8 Hz), 8.44 (0.7 H, dd, J = 4.8, 1.7 Hz), 7.69 - 7.58 (2 H, m), 7.40 (0, 3 H, dd, J = 7.6, 4.9 Hz), 7.33 (1 H, ddd, J = 0.7, 4.8, 7.8 Hz), 7.22 (1 H, m ), 4.65 (0.6 H, s), 4.53 (1.4 H, m), 4.43 (1 H, m), 4.16 (1 H, m), 3.73 ( 1 H, dd, J = 11.6, 7.9 Hz), 3.59 (2 H, m), 3.31 - 3.13 (1 H, m), 2.98 (2 H, s) , 2.79 (1 H, s), 2.85-2.73 (1 H, m). 13

[001526] C NMR (DMSOd6): 168.4, 155.2, 149.1, 148.7, 148.5, 148.3, 135.4, 134.7, 133.1, 132.7, 129.7, 129.6, 129.3, 129.3, 123.7, 123.5, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114.1, 114.1, 113.2, 113.2, 113.1, 113.1, 50.2, 48.5, 48, 35.6, 35.1, 33.4, 29.6, 29.3, 29.2, 29.1.

[001527] Example 135: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (3- (methylsulfonyl) pyrrolidin-1-yl) ethan-1-one

[001528] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light brown powder.

[001529] 1H NMR (DMSOd6): 11.73 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, 2 quin, J = 8.6 Hz), 4.15 (1 H, m), 4.06 (0.4 H, m), 3.95 (0.6 H, m), 3.88 (0.4 H , m), 3.83 (0.4 H, m), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.70-3.61 (1.8 H, m), 3.56 (0.6 H, m), 3.52-3.46 (1.4 H, m), 3.45 (1 H, s), 3.39 (0.4 H, m), 3.22 (1 H, m), 3.06, 3.06, 3.04, 3.04 (3 H, 4 s), 2.84 (1 H, m), 2.33 ( 1 H, m), 2.22 (1 H, m). 13

[001530] C NMR (DMSOd6): 166.4, 166.3, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 155.2, 132.5, 132.4, 129.4, 129.4, 118.8, 118.8, 118.7, 118.6, 118.5, 118.5, 113, 8, 113.8, 113.7, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 60.6, 60.6, 58.9, 58.9, 48, 6, 45.4, 45.4, 45.3, 45.3, 45.1, 44.9, 35.7, 30.3, 30.2, 30.2, 30.2, 29.3, 25.7, 24.1, 24.1.

[001531] Example 136: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (1,1-dioxidothiomorpholine) ethan-1-one

[001532] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001533] 1H NMR (DMSOd6): 11.63 (1 H, s), 7.72 (1 H, td, J = 8.4, 5.8 Hz), 7.17 (1 H, m) , 4.46 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 9.3, 11.1 Hz), 3.87 (4 H, m), 3 , 73 (1 H, dd, J = 11.5, 7.8 Hz), 3.62 (2 H, s), 3.26 (2 H, m), 3.23 (1 H, dd, J = 9.3, 15.8 Hz), 3.10 (2 H, m), 2.84 (1 H, dd, J = 15.8, 8.1 Hz). 13

[001534] C NMR (DMSOd6): 167.4, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.5, 118.7, 113.8, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 51.3, 51.1, 48.6, 43.8, 40.3, 35.7, 29.2, 28.7.

[001535] Example 137: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-thiomorfolinoetan-1-one

[001536] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001537] 1H NMR (DMSOd6): 11.69 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.2, 9.3 Hz), 3.73 (1 H, dd, J = 8.0, 11.6 Hz), 3.71 (4 H, m), 3.51 (2 H, m), 3.21 (1 H, dd, J = 15.8, 9 , 3 Hz), 2.81 (1 H, dd, J = 15.9, 8.0 Hz), 2.61 (2 H, m), 2.55-2.50 (2 H, m). 13

[001538] C NMR (DMSOd6): 166.6, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 132.5, 132.4, 129.3, 118.9, 118.7, 118.6, 114.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.6, 48.1, 44, 35.7, 29.3, 29.1, 26.9, 26.4.

[001539] Example 138: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (2-oxa-7- azaespiro [4.4] nonan-7-yl) etan-1-one

[001540] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a white solid.

[001541] 1H NMR (DMSOd6): 11.71 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.3, 9.4 Hz), 3.81 3.69 (3 H, m), 3.59-3.47 ( 3 H, m), 3.44-3.40 (3 H, m), 3.36 (1 H, m), 3.30-

3.18 (2 H, m), 2.82 (1 H, m), 1.96-1.73 (4 H, m). 13

[001542] C NMR (DMSOd6): 166.4, 166.4, 160.8, 159.2, 157.5, 157.5, 155.9, 155.8, 155.1, 132.4, 132.4, 129.3, 118.9, 118.8, 118.7, 114, 114, 113.8, 113.8, 113.6, 113.6, 104, 104, 103.9, 103, 9, 75.2, 75.2, 75.1, 66.9, 66.9, 55, 54.2, 49.6, 48.6, 47.8, 45.6, 45, 35.8, 35.8, 35.8, 35.6, 34.7, 33.2, 30.3, 30.3, 30, 30, 29.3.

[001543] Example 139: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (pyridin-2-ylmethyl) acetamide

[001544] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[001545] 1H NMR (DMSOd6): 11.84 (1 H, s), 8.58 (1 H, t, J = 5.9 Hz), 8.50 (1 H, m), 7.73 (2 H, m), 7.30 (1 H, d, J = 7.8 Hz), 7.23 (1 H, dd, J = 6.9, 5.0 Hz), 7.17 (1 H, m), 4.43 (1 H, quin, J = m), 4.36 (2 H, m), 4.14 (1 H, dd, J = 9.6, 11.3 Hz), 3.73 (1 H, dd, J = 11.5, 8.1 Hz), 3.36 (2 H, m), 3.17 (1 H, dd, J = 15.8, 9.3 Hz ), 2.78 (1 H, dd, J = 15.7, 8.4 Hz). 13

[001546] C NMR (DMSOd6): 167.9, 160.8, 160.7, 159.1, 159.1, 158.2, 157.5, 157.5, 155.9, 155.9, 155.3, 148.8, 136.7, 132.5, 132.4, 129.2, 122.1, 121.2, 118.6, 118.5, 118.4, 114.1, 113, 8, 113.7, 113.6, 113.6, 104, 104, 103.9, 103.9, 48.5, 44.3, 35.6, 31.5, 29.2.

[001547] Example 140: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-morpholinoetan-1-one

[001548] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light brown powder.

[001549] 1H NMR (DMSOd6): 11.70 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.7 Hz), 7.17 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.15 (1 H, dd, J = 11.5, 9.2 Hz), 3.73 (1 H, dd, J = 11.7, 7.8 Hz), 3.60-3.52 (4 H, m), 3.51 (2 H, s), 3.48-3.40 (4 H, m ), 3.21 (1 H, dd, J = 15.8, 9.3 Hz), 2.82 (1 H, dd, J = 15.8, 8.1 Hz) 13

[001550] C NMR (DMSOd6): 166.8, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.2, 132.5, 132.4, 129.3, 118.9, 118.7, 118.6, 114, 113.8, 113.6, 104.1, 104, 103.9, 103.9, 66, 66, 48.6, 45.7, 41.7, 35.7, 29.3, 28.9.

[001551] Example 141: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-morpholinoetan-1-one

[001552] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light brown powder.

[001553] 1H NMR (DMSOd6): 11.70 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.7 Hz), 7.17 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.15 (1 H, dd, J = 11.5, 9.2 Hz), 3.73 (1 H, dd, J = 11.7, 7.8 Hz), 3.60-3.52 (4 H, m), 3.51 (2 H, s), 3.48-3.40 (4 H, m ), 3.21 (1 H, dd, J = 15.8, 9.3 Hz), 2.82 (1 H, dd, J = 15.8, 8.1 Hz). 13

[001554] C NMR (DMSOd6): 166.8, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.2, 132.5, 132.4, 129.3, 118.9, 118.7, 118.6, 114, 113.8, 113.6, 104.1, 104, 103.9, 103.9, 66, 66, 48.6, 45.7, 41.7, 35.7, 29.3, 28.9.

[001555] Example 142: N- (2- (1H-pyrazol-1-yl) ethyl) -2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo- 2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetamide

[001556] The compound was prepared analogously to Example 25 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo- 2,3,5,5a , 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one (prepared in a similar manner to Example 23, step 1) and isolated as a light yellow solid.

[001557] 1H NMR (DMSOd6): 11.68 (1 H, s), 8.09 (1 H, t, J = 5.6 Hz), 7.68 (1 H, dd, J = 2, 2, 0.6 Hz), 7.63 (1 H, td, J = 8.7, 5.6 Hz), 7.43 (1 H, dd, J = 0.6, 1.8 Hz), 7.21 (1 H, dt, J = 1.4, 9.2 Hz), 6.20 (1 H, m), 4.17 (2 H, t, J = 6.3 Hz), 4, 02 (1 H, d, J = 12.2 Hz), 3.74 (1 H, d, J = 12.2 Hz), 3.44 (2 H, m), 3.31 (2 H, m ), 2.70 (1 H, dd, J = 8.4, 4.4 Hz), 1.65 (1 H, dd, J = 8.2, 5.4 Hz), 1.26 (1 H , t, J = 5.0 Hz). 13

[001558] C NMR (DMSOd6): 168.1, 161.2, 161.2, 159.6, 159.5, 157.8, 157.8, 156.1, 156.1, 155.9, 138.8, 131.5, 130.3, 130.2, 130.1, 117.2, 117.1, 116.9, 115.7, 115.7, 115.6, 115.6, 114, 112.9, 112.9, 112.8, 112.7, 105, 51.4, 50.2, 39.4, 31.3, 26.3, 21.6, 21.2.

[001559] Example 143: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - N- (cyclopropylmethyl) acetamide

[001560] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a yellow solid.

[001561] 1H NMR (DMSOd6): 11.65 (1 H, s), 8.03 (1 H, br t, J = 5.5

Hz), 7.58-7.53 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.07 (1 H, d, J = 12 , 0 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.30 (2 H, m), 2.96 (2 H, t, J = 6.2 Hz), 2 , 82 (1 H, dd, J = 8.4, 4.3 Hz), 1.66 (1 H, dd, J = 8.4, 5.3 Hz), 1.15 (1 H, t, J = 4.8 Hz), 0.90 (1 H, m), 0.40 (2 H, m), 0.16 (2 H, m). 13

[001562] C NMR (DMSOd6): 167.5, 161.7, 160.1, 155.9, 133, 132.9, 132.3, 132.2, 131.7, 129.3, 129, 2, 118, 117.8, 116.2, 116.2, 114, 51.6, 43.2, 31.4, 22, 20.7, 10.7, 3.3, 3.2

[001563] Example 144: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N- (cyanomethyl) acetamide

[001564] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a white solid.

[001565] 1H NMR (DMSOd6): 11.72 (1 H, s), 8.66 (1 H, br t, J = 5.4 Hz), 7.62-7.51 (2 H, m ), 7.24 (1 H, dd, J = 10.0, 8.8 Hz), 4.16 (2 H, m), 4.09 (1 H, dd, J = 11.8 Hz), 3.80 (1 H, d, J = 12.0 Hz), 3.39 (2 H, m), 2.85 (1 H, dd, J = 8.3, 4.2 Hz), 1, 64 (1 H, dd, J = 8.4, 5.3 Hz), 1.18 (1 H, t, J = 4.8 Hz). 13

[001566] C NMR (DMSOd6): 168.6, 161.7, 160.1, 156.2, 132.9, 132.9, 132.3, 132.3, 129.3, 129.2, 118, 117.8, 117.6, 116.2, 112.9, 51.6, 32.3, 30.9, 27.3, 22.1, 20.6.

[001567] Example 145: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) -

N- (2- (pyridin-2-yl) ethyl) acetamide

[001568] The compound was prepared in a manner analogous to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a yellow solid.

[001569] 1H NMR (DMSOd6): 11.66 (1 H, br s), 8.48 (1 H, ddd, J = 0.8, 1.8, 4.8 Hz), 8.03 ( 1 H, t, J = 5.6 Hz), 7.68 (1 H, td, J = 7.6, 1.9 Hz), 7.56 (2 H, m), 7.24 (2 H , m), 7.19 (1 H, ddd, J = 7.5, 4.9, 1.1 Hz), 4.07 (1 H, d, J = 12.2 Hz), 3.79 ( 1 H, d, J = 12.0 Hz), 3.43 (2 H, m), 3.28 (2 H, m), 2.88 (2 H, t, J = 7.3 Hz), 2.79 (1 H, dd, J = 8.4, 4.3 Hz), 1.64 (1 H, dd, J = 8.4, 5.3 Hz), 1.14 (1 H, t , J = 4.8 Hz). 13

[001570] C NMR (DMSOd6): 167.7, 161.8, 160.1, 159, 156, 149, 136.5, 133, 133, 132.3, 132.3, 131.8, 129, 3, 129.2, 123.2, 121.5, 118, 117.8, 116.2, 116.2, 113.8, 51.6, 38.8, 37.2, 32.2, 31, 5, 22, 20.7.

[001571] Example 146: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa hydrochloride [3 , 4] pyrrolo [1,2- c] imidazol-1-yl) -N- (3- (dimethylamino) propyl) acetamide

[001572] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a dark yellow solid.

[001573] 1H NMR (D2O): 7.52 (1 H, dd, J = 6.6, 2.3 Hz), 7.43 (1 H, m), 7.03 (1 H, t, J = 9.4 Hz), 4.20 (1 H, d, J = 12.2 Hz), 3.92 (1 H, d, J = 12.2 Hz), 3.58 (2 H, s ), 3.30 (2 H, t, J = 6.7 Hz), 3.14 (2 H, m), 2.87 (6 H, s), 2.73 (1 H, dd, J = 8.4, 4.3 Hz), 1.95 (2 H, m), 1.66 (1 H, dd, J = 8.1, 5.8 Hz), 1.19 (1 H, t, J = 4.8 Hz). 13

[001574] C NMR (D2O): 171.6, 162, 160.3, 151.4, 134.7, 133.1, 132.5, 132.4, 128.3, 128.2, 117, 6, 117.4, 116.1, 114.3, 55.3, 52.2, 42.7, 36.3, 32.4, 31.3, 24.1, 21.5, 20.5.

[001575] Example 147: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - 1- (4- (pyridin-2-yl) piperazin-1-yl) etan-1-one

[001576] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a yellow solid.

[001577] 1H NMR (DMSOd6): 11.63 (1 H, s), 8.11 (1 H, dd, J = 5.1, 1.2 Hz), 7.68 (1 H, br d , J = 18.6 Hz), 7.56 (2 H, m), 7.23 (1 H, dd, J = 10.1, 8.8 Hz), 6.99 (1 H, br s) , 6.75 (1 H, br s), 4.08 (1 H, br d, J = 12.2 Hz), 3.79 (1 H, d, J = 12.0 Hz), 3.69 -3.51 (10 H, m), 2.80 (1 H, dd, J = 8.3, 4.2 Hz), 1.68 (1 H, dd, J = 8.4, 5.3 Hz), 1.11 (1 H, br t, J = 4.8 Hz). 13

[001578] C NMR (DMSOd6): 167, 161.8, 160.1, 156, 133, 133, 132.3, 132.3, 131.8, 129.3, 129.2, 118, 117, 8, 116.2, 116.2, 113.7, 113.2, 51.6, 44.9, 44.6, 44.4, 40.8, 32.3, 29.2, 22.1, 20.7.

[001579] Example 148: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N- (tetrahydrofuran-3-yl) acetamide

[001580] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige foam.

[001581] 1H NMR (DMSOd6): 11.66 (1 H, s), 8.23 (1 H, d, J = 6.7 Hz), 7.56 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.6 Hz), 4.24 (1 H, tt, J = 10.2, 3.8 Hz), 4.07 (1 H, d, J = 12.0 Hz), 3.78 (2 H, m), 3.74 (1 H, dd, J = 8.9, 6.0 Hz), 3.67 (1 H, td, J = 8, 2, 5.6 Hz), 3.49 (1 H, dd, J = 8.8, 3.7 Hz),

3.30 (2 H, m), 2.81 (1 H, dd, J = 8.4, 4.2 Hz), 2.08 (1 H, dq, J = 12.6, 7.6 Hz ), 1.75 (1 H, m), 1.66 (1 H, dd, J = 8.4, 5.4 Hz), 1.12 (1 H, t, J = 4.8 Hz).

[001582] 13C NMR (DMSOd6): 167.6, 161.8, 160.1, 155.9, 133, 133, 132.3, 132.2, 131.7, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 113.9, 72.4, 66.3, 51.6, 49.8, 32.2, 32, 31.2, 22.1, 20, 7.

[001583] Example 149: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - 1- (4,4-difluoropiperidin-1-yl) etan-1-one

[001584] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo- 2,3,5,5a , 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a brown solid .

[001585] 1H NMR (DMSOd6): 11.63 (1 H, br s), 7.63 (1 H, td, J = 8.7, 5.7 Hz), 7.20 (1 H, dt , J = 9.3 Hz, 1.3 Hz), 4.04 (1 H, d, J = 12.2 Hz), 3.74 (1 H, d, J = 12.2 Hz), 3, 66 (2 H, m), 3.59 (4 H, m), 2.69 (1 H, dd, J = 8.4, 4.4 Hz), 2.04 (2 H, m), 1 , 93 (2 H, m), 1.68 (1 H, dd, J = 8.2, 5.4 Hz), 1.24 (1 H, t, J = 5.0 Hz). 13

[001586] C NMR (DMSOd6): 166.8, 161.2, 161.2, 159.6, 159.5, 157.8, 157.7, 156.1, 156.1, 156, 131, 5, 130.3, 130.2, 124.3, 122.7, 121.1, 117.1, 117, 116.9, 115.7, 115.7, 115.6, 115.6, 114, 112.9, 112.9, 112.8, 112.7, 51.4, 42.2, 42.1, 42.1, 38.5, 38.5, 38.4, 33.9, 33, 8, 33.6, 33.3, 33.2, 33, 29.1, 26.4, 21.7, 21.2.

[001587] Example 150: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N- (2,2,2-trifluoroethyl) acetamide

[001588] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo- 2,3,5,5a , 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a brown solid -clear.

[001589] 1H NMR (DMSOd6): 11.73 (1 H, s), 8.67 (1 H, t, J = 6.3 Hz), 7.63 (1 H, td, J = 8, 7, 5.6 Hz), 7.21 (1 H, dt, J = 1.4, 9.2 Hz), 4.03 (1 H, d, J = 12.2 Hz), 3.93 ( 2 H, qd, J = 9.8, 6.5 Hz), 3.74 (1 H, d, J = 12.2 Hz), 3.43 (2 H, m), 2.72 (1 H , dd, J = 8.4, 4.4 Hz), 1.65 (1 H, dd, J = 8.4, 5.4 Hz), 1.26 (1 H, t, J = 5.0 Hz).

[001590] 13C NMR (DMSOd6): 169.2, 161.7, 161.6, 160, 160, 158.3, 158.2, 156.6, 156.6, 156.5, 132.2, 130.8, 130.7, 127.9, 126.1, 124.2, 122.4, 117.6, 117.5, 117.4, 116.2, 116.2, 116.1, 116, 1, 114, 113.4, 113.4, 113.2, 113.2, 51.9, 40.1, 31.5, 26.8, 22.1, 21.7.

[001591] Example 151: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N- (pyridin-3-ylmethyl) acetamide

[001592] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo- 2,3,5,5a , 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a white solid .

[001593] 1H NMR (DMSOd6): 11.75 (1 H, s), 8.55-8.48 (2 H, m), 8.43 (1 H, dd, J = 4.7, 1 , 6 Hz), 7.67 (1 H, dt, J = 7.8, 2.0 Hz), 7.64 (1 H, td, J = 8.7, 5.7 Hz), 7.34 (1 H, ddd, J = 0.7, 4.8, 7.8 Hz), 7.21 (1 H, dt, J = 1.0, 9.1 Hz), 4.32 (2 H, m), 4.02 (1 H, d, J = 12.2 Hz), 3.74 (1 H, d, J = 12.2 Hz), 3.40 (2 H, m), 2.68 (1 H, dd, J = 8.4, 4.4 Hz), 1.62 (1 H, dd, J = 8.3, 5.5 Hz), 1.27 (1 H, t, J = 5.0 Hz). 13

[001594] C NMR (DMSOd6): 168, 161.2, 161.2, 159.6, 159.5, 157.8, 157.7, 156.1, 156, 148.8, 148.1, 135.1, 134.7, 131.6, 130.3, 130.2, 123.4, 117.2, 117, 116.9, 115.7, 115.6, 114, 112.9, 112, 9, 112.8, 112.8, 51.4, 39.8, 31.3, 26.3, 21.5, 21.2.

[001595] Example 152: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N- (2,2,2-trifluoroethyl) acetamide

[001596] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a light beige solid .

[001597] 1H NMR (DMSOd6): 11.75 (1 H, s), 8.55-8.48 (2 H, m), 8.43 (1 H, dd, J = 4.7, 1 , 6 Hz), 7.67 (1 H, dt, J = 7.8, 2.0 Hz), 7.64 (1 H, td, J = 8.7, 5.7 Hz), 7.34 (1 H, ddd, J = 0.7, 4.8, 7.8 Hz), 7.21 (1 H, dt, J = 1.0, 9.1 Hz), 4.32 (2 H, m), 4.02 (1 H, d, J = 12.2 Hz), 3.74 (1 H, d, J = 12.2 Hz), 3.40 (2 H, m), 2.68 (1 H, dd, J = 8.4, 4.4 Hz), 1.62 (1 H, dd, J = 8.3, 5.5 Hz), 1.27 (1 H, t, J = 5.0 Hz). 13

[001598] C NMR (DMSOd6): 168, 161.2, 161.2, 159.6, 159.5, 157.8, 157.7, 156.1, 156, 148.8, 148.1, 135.1, 134.7, 131.6, 130.3, 130.2, 123.4, 117.2, 117, 116.9, 115.7, 115.6, 114, 112.9, 112, 9, 112.8, 112.8, 51.4, 39.8, 31.3, 26.3, 21.5, 21.2.

[001599] Example 153: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - N-cyclobutylacetamide

[001600] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a yellow solid.

[001601] 1H NMR (DMSOd6): 11.63 (1 H, s), 8.20 (1 H, br d, J = 7.8 Hz), 7.56 (2 H, m), 7, 24 (1 H, dd, J = 9.9, 8.7 Hz), 4.20 (1 H, sxt, J = 8.1 Hz), 4.07 (1 H, d, J = 12.0 Hz), 3.78 (1 H, d, J = 12.0 Hz), 3.25 (2 H, m), 2.80 (1 H, dd, J = 8.4, 4.3 Hz) , 2.14 (2 H, m), 1.90 (2 H, m), 1.63 (3 H, m), 1.13 (1 H, t, J = 4.8 Hz). 13

[001602] C NMR (DMSOd6): 166.6, 161.7, 160.1, 155.9, 133, 132.9, 132.3, 132.2, 131.7, 129.3, 129, 2, 118, 117.8, 116.2, 113.9, 51.5, 44.1, 32.2, 31.3, 30.2, 30.2, 22, 20.7, 14.6.

[001603] Example 154: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - N-cyclopropylacetamide

[001604] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a yellow solid.

[001605] 1H NMR (DMSOd6): 11.63 (1 H, s), 8.04 (1 H, br d, J = 3.8 Hz), 7.56 (2 H, m), 7, 24 (1 H, dd, J = 10.1, 8.7 Hz), 4.07 (1 H, d, J = 11.9 Hz), 3.78 (1 H, d, J = 12.0 Hz), 3.25 (2 H, m), 2.81 (1 H, dd, J = 8.3, 4.2 Hz), 2.62 (1 H, m), 1.65 (1 H , dd, J = 8.4, 5.3 Hz), 1.13 (1 H, t, J = 4.8

Hz), 0.62 (2 H, m), 0.42 (2 H, m). 13

[001606] C NMR (DMSOd6): 168.8, 161.7, 160.1, 155.9, 133, 132.9, 132.3, 132.2, 131.7, 129.3, 129, 2, 118, 117.8, 116.2, 116.2, 113.8, 51.6, 32.2, 31.2, 22.5, 22, 20.7, 5.6, 5.6.

[001607] Example 155: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - N-cyclopentyl-N-methylacetamide

[001608] The compound was prepared in a manner analogous to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a brown solid.

[001609] 1H NMR (DMSOd6): 11.59 (1 H, br s), 7.55 (2 H, m), 7.24 (1 H, t, J = 9.4 Hz), 4, 82, 4.28 (1 H, 2 m), 4.07 (1 H, d, J = 12.0 Hz), 3.78 (1 H, d, J = 12.0 Hz), 3.61 , 3.52 (2 H, 2 m), 2.85, 2.70 (3 H, 2 s), 2.77 (1 H, m), 1.85-1.40 (9 H, m) , 1.10 (1 H, m). 13

[001610] C NMR (DMSOd6): 167.9, 167.7, 161.7, 160.1, 155.9, 155.9, 133, 132.9, 132.3, 132.2, 131, 6, 131.6, 129.3, 129.2, 118, 117.8, 116.2, 116.1, 114.1, 114, 57.6, 53.7, 51.5, 32.3, 32.2, 30.1, 29.5, 29.4, 28.5, 27.8, 27.7, 27.1, 23.9, 23.8, 22.1, 20.7, 20, 6.

[001611] Example 156: N-benzyl-2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2-c] imidazol-1-yl) acetamide

[001612] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6 , 6a hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a brown solid.

[001613] 1H NMR (DMSOd6): 11.72 (1 H, s), 8.45 (1 H, t, J = 5.9 Hz), 7.47-7.40 (2 H, m) , 7.35-7.25 (5 H, m), 7.22 (1 H, m), 4.29 (2 H, m), 4.07 (1 H, d, J = 12.0 Hz ), 3.80 (1 H, d, J = 12.2 Hz), 3.38 (2 H, m), 2.77 (1 H, dd, J = 8.4, 4.3 Hz), 1.62 (1 H, dd, J = 8.4, 5.3 Hz), 1.16 (1 H, m). 13

[001614] C NMR (DMSOd6): 167.8, 161.2, 159.6, 156, 139.3, 131.8, 130.1, 130, 129.3, 129.2, 128.9, 128.8, 128.2, 128.2, 128.2, 127.3, 126.8, 117.6, 117.4, 113.7, 51.5, 42.3, 32.3, 31, 4, 22, 20.7.

[001615] Example 157: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - 1-morpholinoetan-1-one

[001616] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1-

(1H-imidazol-1-yl) ethan-1-one and isolated as a green solid.

[001617] 1H NMR (DMSOd6): 11.61 (1 H, s), 7.65-7.46 (2 H, m), 7.24 (1 H, dd, J = 10.0, 8 , 7 Hz), 4.08 (1 H, d, J = 12.0 Hz), 3.79 (1 H, d, J = 12.0 Hz), 3.63-3.52 (6 H, m), 3.49 (2 H, m), 3.46 (2 H, m), 2.78 (1 H, dd, J = 8.4, 4.3 Hz), 1.68 (1 H , dd, J = 8.3, 5.4 Hz), 1.11 (1 H, t, J = 4.8 Hz). 13

[001618] C NMR (DMSOd6): 166.9, 161.8, 160.1, 156, 133, 133, 132.3, 132.3, 131.7, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 113.7, 66, 51.6, 51.6, 45.7, 41.7, 32.3, 29, 22.1, 20.7.

[001619] Example 158: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrole [1,2-c] imidazol-1-yl) - 1- (piperidin-1-yl) ethan-1-one

[001620] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6 , 6a- hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a dark yellow solid .

[001621] 1H NMR (DMSOd6): 11.60 (1 H, s), 7.47-7.40 (2 H, m), 7.30 (1 H, dd, J = 9.9, 8 , 7 Hz), 4.08 (1 H, d, J = 12.2 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.54 (2 H, m), 3 , 44 (4 H, m), 2.78 (1 H, dd, J = 8.3, 4.2 Hz), 1.68 (1 H, dd, J = 8.4, 5.3 Hz) , 1.58 (2 H, m), 1.50 (2 H, m), 1.44 (2 H, m), 1.10 (1 H, t, J = 4.8 Hz). 13

[001622] C NMR (DMSOd6): 166.2, 161.2, 159.6, 155.9, 131.6, 130.1, 130.1, 129.3, 129.3, 128.9, 128.7, 128.3, 128.2, 117.6, 117.4, 114, 51.5, 51.5, 46.2, 42.2, 32.3, 29.3, 25.9, 25.2, 23.9, 22.1, 20.7.

[001623] Example 159: (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-

2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (cyanomethyl) acetamide

[001624] The compound was prepared analogously to Example 34 from (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 13) and isolated as a gray powder.

[001625] 1H NMR (DMSOd6): 11.80 (1 H, s), 8.65 (1 H, t, J = 5.5 Hz), 7.72 (1 H, m), 7.17 (1 H, m), 4.45 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 9.4, 11.5 Hz), 4.14 (2 H, d, J = 5.6 Hz), 3.74 (1 H, dd, J = 11.5, 8.1 Hz), 3.34 (2 H, m), 3.22 (1 H, dd, J = 15.8, 9.3 Hz), 2.86 (1 H, dd, J = 15.8, 8.4 Hz). 13

[001626] C NMR (DMSOd6): 168.6, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.4, 132.5, 132.4, 129.7, 118.6, 118.5, 118.3, 117.5, 113.8, 113.8, 113.6, 113.6, 113.3, 104, 1, 104, 103.9, 103.9, 48.6, 35.7, 31, 29.2, 27.2.

[001627] Example 160: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((1R, 2R) -2-hydroxycyclohexyl) acetamide

[001628] The compound was prepared in an analogous manner to Example 34 from (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 13) and isolated as a beige powder.

[001629] 1H NMR (DMSOd6): 11.71 (1 H, 2 s), 7.80 (1 H, 2 d, J = 2.1 Hz), 7.72 (1 H, m), 7 , 16 (1 H, m), 4.52 (1 H, 2 dd, J = 4.8 Hz), 4.43 (1 H, 2 quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.5 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.37 (1 H, m), 3.29 - 3.18 (4 H, m), 2.86 (0.5 H, dd, J = 8.2, 16.2 Hz), 2.82 (0.5 H, dd, J = 8.3 , 16.0 Hz), 1.83 (1 H, m), 1.75 (1 H, m), 1.64-1.50 (2 H, 2 m), 1.22-1.01 ( 4 H, m). 13

[001630] C NMR (DMSOd6): 167.2, 167.2, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155, 155, 132.5, 132.4, 129, 129, 118.8, 118.8, 118.7, 118.6, 118.6, 118.5, 114.6, 113.8, 113, 8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 71.1, 54.5, 48.5, 35.6, 33.9, 31.8, 31, 7, 30.9, 29.4, 29.4, 24.1, 23.7.

[001631] Example 161: 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((1S, 2S) -2-hydroxycyclopentyl) acetamide

[001632] The compound was prepared analogously to Example 34 from (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 13) and isolated as a light brown powder.

[001633] 1H NMR (DMSOd6): 11.74 (1 H, s), 7.89 (1 H, d, J = 7.2 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.70 (1 H, d, J = 4.3 Hz), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.3 Hz), 3.79 (1 H, m), 3.73 (2 H, m), 3.22 (2 H, s), 3.22 (1 H, m ), 2.83 (1 H, dd, J = 15.8, 8.2 Hz), 1.90 (1 H, m), 1.76 (1 H, m), 1.59 (2 H, m), 1.41 (1 H, m), 1.30 (1 H, m). 13

[001634] C NMR (DMSOd6): 167.3, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 128.9, 118.8, 118.7, 118.5, 114.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 76, 57.7, 48.5, 35.6, 32.1, 31.5, 29.4, 29.3, 20.4.

[001635] Example 162: (S) -N- (2- (1H-pyrazol-1-yl) ethyl) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2, 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[001636] The compound was prepared analogously to Example 34 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a beige solid.

[001637] 1H NMR (DMSOd6): 11.74 (1 H, s), 8.06 (1 H, t, J = 5.6 Hz), 7.66 (1 H, d, J = 2, 1 Hz), 7.62 (1 H, m), 7.40 (1 H, d, J = 1.3 Hz), 7.23 (1 H, m), 6.17 (1 H, t, J = 2.1 Hz), 4.42 (1 H, quin, J = 8.7 Hz), 4.15 (3 H, m), 3.73 (1 H, dd, J = 11.4, 8.2 Hz), 3.43 (2 H, q, J = 6.0 Hz), 3.22 (2 H, m), 3.13 (1 H, dd, J = 15.7, 9, 2 Hz), 2.79 (1 H, dd, J = 15.8, 8.4 Hz). 13

[001638] C NMR (DMSOd6): 168, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 155, 154.9, 138.7, 130.1, 129.7, 129.6, 129.2, 118.4, 116.1, 116, 115.9, 115.9, 114, 113.2, 113.2, 113.1, 113, 1, 104.9, 50.2, 48.4, 39.8, 35.6, 31.4, 29.1.

[001639] Example 163: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (1,1-dioxidotetrahydro-2H-thiopyran-4-yl) -N-methylacetamide

The compound was prepared analogously to Example 34 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an orange solid.

[001641] 1H NMR (DMSOd6): 11.70 (1 H, s), 7.61 (1 H, m), 7.22 (1 H, m), 4.58 (0.65 H, tt , J = 12.3, 3.4 Hz), 4.45 (1 H, m), 4.16 (1.35 H, m), 3.74 (1 H, m), 3.58 (0 , 7 H, m), 3.49 (1.3 H, m), 3.43-3.35 (2 H, m), 3.22

(1 H, m), 3.12 (0.7 H, m), 3.04 (1.3 H, m), 2.85 (1.95 H, s), 2.83 (1 H, m), 2.70 (1.05 H, s), 2.24-2.07 (2 H, m), 1.93 (0.7 H, m), 1.79 (1.3 H, m). 13

[001642] C NMR (DMSOd6): 167.8, 167.6, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.1, 155.1, 154.9, 154.8, 129.7, 129.6, 129.5, 129.3, 118.9, 118.8, 118.7, 116.1, 116, 115.9, 115.9, 114.2, 114.1, 113.2, 113.2, 113.1, 113.1, 49.4, 49.3, 49.2, 48.6, 35.7, 35.6, 29, 9, 29.4, 29.2, 29.1, 27.7, 27.7, 26.9, 26.6.

[001643] Example 164: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (3- (methylsulfonyl) pyrrolidin-1-yl) ethan-1-one

[001644] The compound was prepared in an analogous way to Example 34 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 12) and isolated as a beige solid.

[001645] 1H NMR (DMSOd6): 11.73 (1 H, 2 s), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, m) , 4.15 (1 H, m), 4.06, 3.94 (1 H, 2 m), 3.88, 3.83, 3.70-3.61, 3.56, 3.50, 3.38 (4 H, several mult.), 3.72 (1 H, dd, J = 11.4, 8.0 Hz), 3.48, 3.45 (2 H, 2 m), 3, 22 (1 H, dd, J = 15.6, 9.4 Hz), 3.07, 3.05 (3 H, 2s), 2.84 (1 H, m), 2.33 (1 H, m), 2.22 (1 H, m). 13

[001646] C NMR (DMSOd6): 166.4, 166.3, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 155.2, 132.5, 132.4, 129.4, 129.4, 118.8, 118.8, 118.7, 118.6, 118.5, 118.5, 113, 8, 113.8, 113.7,

113.6, 113.6, 104.1, 104, 103.9, 103.9, 60.6, 60.6, 58.9, 58.9, 48.6, 45.4, 45.4, 45.3, 45.3, 45.1, 44.9, 35.7, 30.3, 30.2, 30.2, 30.2, 29.3, 25.7, 24.1, 24, 1.

[001647] Example 165: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (2-oxa-8- azaespiro [4.5] decan-8-yl) etan-1-one

[001648] The compound was prepared analogously to Example 34 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 12) and isolated as a beige solid.

[001649] 1H NMR (DMSOd6): 11.70 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.3 Hz), 4.15 (1 H, br t, J = 10 Hz), 3.73 (3 H, m), 3.60-3.27 (8 H, m), 3.21 (1 H, br dd, J = 15.7, 9.2 Hz), 2.80 (1 H, br dd, J = 15.8, 7.6 Hz), 1.72 (2 H, m) , 1.47 (2 H, m), 1.42 (2 H, m). 13

[001650] C NMR (DMSOd6): 166.4, 166.4, 160.8, 159.2, 157.5, 157.5, 155.9, 155.8, 155.1, 132.4, 132.4, 129.1, 118.9, 118.8, 118.7, 114, 114, 113.8, 113.8, 113.6, 113.6, 104, 104, 103.9, 103, 9, 76.9, 76.7, 66.4, 66.4, 48.6, 43.4, 41.6, 36.5, 36.3, 35.6, 34.7, 34, 29, 3, 29.2.

[001651] Example 166: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (1-oxothiomorpholine) ethan-1-one

[001652] The compound was prepared analogously to Example 34 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 12) and isolated as a beige solid.

[001653] 1H NMR (DMSOd6): 11.68 (1 H, s), 7.72 (1 H, m), 7.17 (1 H, m), 4.46 (1 H, quin, J = 8.4 Hz), 4.16 (2 H, m), 3.88 (1 H, m), 3.82 (1 H, m), 3.73 (1 H, dd, J = 11, 3, 8.1 Hz), 3.57 (3 H, m), 3.23 (1 H, dd, J = 15.7, 9.4 Hz), 2.90 (1 H, m), 2 , 83 (1 H, dd, J = 15.8, 8.2 Hz), 2.76 (3 H, m). 13

[001654] C NMR (DMSOd6): 167, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 132, 5, 132.4, 129.4, 118.9, 118.7, 118.6, 113.9, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103, 9, 103.9, 48.6, 45.1, 45, 44.7, 44.6, 37, 37, 37, 35.7, 33.1, 33.1, 29.3, 29.3, 29.2, 28.8, 28.8.

[001655] Example 167: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[001656] The compound was prepared in an analogous manner to Example 34 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 12) and isolated as a brown powder.

[001657] 1H NMR (DMSOd6): 11.68 (1 H, 2 s), 7.72 (1 H, m), 7.16 (1 H, m), 5.08 (0.6 H, m), 4.61 (0.4 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 9.6, 11.5 Hz), 3.91 (1 H, m), 3.72 (1 H, dd, J = 11.7, 7.8 Hz), 3.66 (0.8 H, m), 3.63- 3.52 (3 H, m), 3.48 (1.2 H, m), 3.20 (1 H, m), 2.88 (1.8 H, m), 2.81 (1 H , m), 2.72 (1.2 H, s), 2.21 - 2.02 (1 H, m), 1.88-1.69 (1 H, m). 13

[001658] C NMR (DMSOd6): 168.2, 168.2, 167.7, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 155.1, 132.4, 132.4, 129.3, 129.2, 118.8, 118.7, 118.6, 114.2, 114.2, 114, 1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 69.3, 69.3, 69.2, 67.1, 67, 56.5, 56.5, 52.9, 48.6, 35.7, 30, 29.8, 29.8, 29.7, 29.7, 29.5, 29.5, 29.3, 29.2, 27.6.

[001659] Example 168: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (1,3,4-thiadiazol-2-yl) acetamide

[001660] To a stirred mixture of 1,3,4-thiadiazole-2-amine (35.2 mg, 0.348 mmol) and N-ethyl-N-isopropylpropan-2-amine (DIPEA) (0.06 mL, 0.348 mmol) in dichloromethane (2 mL) (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H- pyrrole [1,2-c] imidazol-1-yl) acetic (100 mg, 0.290 mmol) followed by the addition of 2,4,6-trioxide, 2,4,6-tripropyl-1,3,5,2, 4,6-trioxatrifosfinane (0.180 mL, 0.290 mmol). The reaction was stirred at room temperature overnight. After that, the organic was removed in vacuo and the residue was purified by column chromatography in a mixture of dichloromethane - methanol. Recrystallization from isopropanol gave the title product as an off-white solid. Yield: 76 mg, 61%.

[001661] 1H NMR (DMSOd6): 12.72 (1 H, s), 11.81 (1 H, s), 9.17 (1 H, s), 7.61 (1 H, m), 7.22 (1 H, m), 4.47 (1 H, quin, J = 8.6 Hz), 4.17 (1 H, dd, J = 9.5, 11.2 Hz), 3, 75 (1 H, dd, J = 11.7, 8.1 Hz), 3.71 (2 H, m), 3.26 (1 H, dd, J = 15.8, 9.2 Hz), 2.88 (1 H, dd, J = 15.8, 8.2 Hz). 13

[001662] C NMR (DMSOd6): 167.5, 160.2, 160.1, 158.5, 158.5, 158.5, 156.6, 156.5, 155.6, 154.9, 154.9, 148.8, 130.2, 129.7, 129.6, 118.7, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 112.5, 48.6, 35.6, 31.1, 29.2.

[001663] Example 169: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (pyridin-2-yl) acetamide

[001664] The compound was prepared analogously to Example 168 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white powder.

[001665] 1H NMR (DMSOd6): 11.81 (1 H, s), 10.61 (1 H, s), 8.31 (1 H, ddd, J = 0.8, 1.8, 4 , 8 Hz), 8.04 (1 H, br d, J = 8.2 Hz), 7.77 (1 H, m), 7.61 (1 H, m), 7.21 (1 H, m), 7.10 (1 H, ddd, J = 7.3, 4.9, 0.9 Hz), 4.46 (1 H, quin, J = 8.6 Hz), 4.17 (1 H, dd, J = 11.3, 9.4 Hz), 3.75 (1 H, dd, J = 11.6, 7.9 Hz), 3.58 (2 H, m), 3.26 (1 H, dd, J = 15.8, 9.3 Hz), 2.88 (1 H, dd, J = 8.3, 15.8 Hz). 13

[001666] C NMR (DMSOd6): 167.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.4, 154.9, 154.9, 151.9, 148, 138.2, 129.7, 129.6, 119.5, 118.8, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 113, 6, 113.4, 113.2, 113.2, 113.1, 113.1, 48.6, 35.6, 32.2, 29.2.

[001667] Example 170: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N- (pyridin-2-yl) acetamide

[001668] The compound was prepared analogously to Example 168 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a acid, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic and isolated as a brown solid.

[001669] 1H NMR (DMSOd6): 11.71 (1 H, s), 10.62 (1 H, s), 8.33 (1 H, dd, J = 4.7, 1.0 Hz) , 8.06 (1 H, br d, J = 8.1 Hz), 7.79 (1 H, m), 7.56 (2 H, m), 7.24 (1 H, dd, J = 10.0, 8.8 Hz), 7.11 (1 H, ddd, J = 6.7, 5.6, 0.7 Hz), 4.09 (1 H, d, J = 12.0 Hz ), 3.81 (1 H, d, J = 12.2 Hz), 3.65 (2 H, m), 2.88 (1 H, dd, J = 8.4, 4.3 Hz), 1.66 (1 H, dd, J = 8.3, 5.4 Hz), 1.14 (1 H, t, J = 4.8 Hz). 13

[001670] C NMR (DMSOd6): 167.7, 161.7, 160.1, 156.1, 151.9, 148, 138.2, 132.9, 132.9, 132.3, 132, 3, 129.3, 129.2, 119.5, 118, 117.8, 116.2, 116.2, 113.4, 113.2, 51.6, 32.3, 32.2, 22, 2, 20.6.

[001671] Example 171: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4 ] pyrrolo [1,2-c] imidazol-1-yl) - N- (pyridin-3-yl) acetamide

[001672] The compound was prepared analogously to Example 168 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo- 2,3,5,5a acid, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic and isolated as a beige solid.

[001673] 1H NMR (DMSOd6): 11.75 (1 H, br s), 10.33 (1 H, br s), 8.75 (1 H, br s), 8.27 (1 H, d, J = 4.1 Hz), 8.04 (1 H, d, J = 7.9 Hz), 7.46 (1 H, dd, J = 6.5, 2.6 Hz), 7, 43 (1 H, ddd, J = 8.7, 4.3, 2.6 Hz), 7.37 (1

H, dd, J = 8.2, 4.7 Hz), 7.30 (1 H, dd, J = 9.0, 10.0 Hz), 4.10 (1 H, d, J = 12, 0 Hz), 3.82 (1 H, d, J = 12.0 Hz), 3.61 (2 H, br s), 2.88 (1 H, dd, J = 8.2, 4.1 Hz), 1.67 (1 H, dd, J = 8.4, 5.4 Hz), 1.16 (1 H, t, J = 4.8 Hz). 13

[001674] C NMR (DMSOd6): 167.4, 161.3, 159.6, 156.2, 144.3, 140.8, 135.7, 132.3, 130.2, 130.1, 129.4, 129.3, 128.9, 128.7, 128.3, 126.3, 123.7, 117.6, 117.4, 113.2, 51.6, 32.4, 32, 1, 22.1, 20.7.

[001675] Example 172: (R) -1- (2-hydroxyethyl) -6- (2,3,5,6-tetrafluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazole-3-thione

[001676] The compound was prepared analogously to Example 8 from (R) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethyl acetate and isolated as a cream powder.

[001677] 1H NMR (DMSOd6): 11.73 (1 H, s), 7.85 (1 H, m), 4.69 (1 H, t, J = 5.3 Hz), 4.48 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.5, 9.2 Hz), 3.76 (1 H, dd, J = 11.6, 8.1 Hz), 3.55 (2 H, m), 3.29 (1 H, dd, J = 15.6, 9.2 Hz), 2.93 (1 H, dd, J = 15, 6, 8.2 Hz), 2.49 (2H, t, J = 6.8 Hz). 13

[001678] C NMR (DMSOd6): 155, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145, 3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.2, 120.4, 120.3, 120.2, 117.6, 105, 9, 105.7, 105.5, 59.2, 48.3, 35.8, 29, 28.

[001679] Example 173: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2-hydroxyethyl) -2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazole-3-thione

[001680] The compound was prepared in an analogous manner to Example 8 from (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) ethyl acetate and isolated as a light cream powder.

[001681] 1H NMR (DMSOd6): 11.72 (1 H, s), 7.72 (1 H, ddd, J = 9.0, 8.0, 5.8 Hz), 7.16 (1 Hm), 4.69 (1 H, br t, J = 5.1 Hz), 4.43 (1 H, quin, J = 8.7 Hz), 4.13 (1 H, dd, J = 11 , 6, 9.1 Hz), 3.71 (1 H, dd, J = 11.6, 8.1 Hz), 3.54 (2 H, m), 3.25 (1 H, dd, J = 15.6, 9.2 Hz), 2.89 (1 H, dd, J = 15.6, 8.4 Hz), 2.48 (2 H, t, J = 6.7 Hz). 13

[001682] C NMR (DMSOd6): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 154.9, 132.5, 132.4, 128.3, 118.7, 118.6, 118.4, 117.5, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 59.2, 48.4, 35.7, 29.1, 28.

[001683] Example 174: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -1- (2-morpholinoethyl) -5.5a, 6.6a-tetrahydrocyclopropa hydrochloride [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001684] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6 , 6a- hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) -1-morpholinoethane-1-

ona (Example 66) and isolated as a beige solid.

[001685] 1H NMR (CD3OD): 7.44 (1 H, dd, J = 6.4, 2.7 Hz), 7.36 (1 H, ddd, J = 8.8, 4.4, 2.6 Hz), 7.17 (1 H, dd, J = 9.8, 8.8 Hz), 4.20 (1 H, d, J = 12.3 Hz), 3.93 (1 H , d, J = 12.2 Hz), 3.86 (4 H, br), 3.28-3.0 (6 H, m), 2.94 (2 H, m), 2.85 (1 H, dd, J = 8.3, 4.0 Hz), 1.71 (1 H, dd, J = 8.2, 5.6 Hz), 1.18 (1 H, dd, J = 5, 5, 4.2 Hz). 13

[001686] C NMR (CD3OD): 163.3, 161.6, 157.1, 134.2, 131.5, 131.4, 131, 130.9, 130.7, 130.7, 130, 129.9, 118.6, 118.4, 66.2, 57.3, 54, 53.5, 53.5, 34.2, 23.2, 22.1, 21.3.

[001687] Example 175: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -1- (2- (isopropylamino) ethyl) -5.5a, 6.6a-tetrahydrocyclopropa hydrochloride [3 , 4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001688] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6 , 6a hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N-isopropylacetamide (Example 67) and isolated as a light beige solid.

[001689] 1H NMR (DMSOd6): 11.80 (1 H, br s), 8.48 (2 H, br s), 7.48 (1 H, dd, J = 6.5, 2.7 Hz), 7.44 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.31 (1 H, dd, J = 9.9, 8.9 Hz), 4 , 08 (1 H, d, J = 12.2 Hz), 3.80 (1 H, d, J = 12.0 Hz), 3.31 (1 H, m), 3.16 (2 H, br t, J = 7.5 Hz), 2.97 (1 H, dd, J = 8.4, 4.3 Hz), 2.80 (2 H, m), 1.67 (1 H, dd , J = 8.2, 5.3 Hz), 1.23 (6 H, d, J = 6.5 Hz), 1.20 (1 H, t, J = 4.8 Hz). 13

[001690] C NMR (DMSOd6): 161.2, 159.6, 156.5, 131.7, 130.1,

130.1, 129.4, 129.3, 128.8, 128.7, 128.3, 128.3, 117.6, 117.4, 114.6, 51.5, 51.5, 49, 4, 42.3, 32.5, 22.1, 21.4, 20.3, 18.8, 18.8.

[001691] Example 176: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2 - ((((R) - tetrahydrofuran-3-yl) amino) ethyl) -2, 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[001692] The compound was prepared analogously to Example 35 from 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra - hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide (Example 116) and isolated as a cream powder.

[001693] 1H NMR (DMSOd6): 11.72 (1 H, br s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.13 (1 H, dd, J = 11.0, 9.7 Hz), 3.74-3.68 (2 H, m), 3.66 (1 H, dd, J = 8.6, 5.8 Hz), 3.61 (1 H, m), 3.33 (1 H, m), 3.31 - 3.21 (2 H, m), 2, 88 (1 H, dd, J = 15.6, 8.2 Hz), 2.67 (2 H, m), 2.46 (2 H, t, J = 7.1 Hz), 1.91 ( 1 H, m), 1.59 (1 H, m). 13

[001694] C NMR (DMSOd6): 160.8, 160.8, 159.2, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 154.9, 132.4, 132.4, 128.1, 118.9, 118.7, 118.6, 118.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 72.5, 66.3, 57.9, 48.4, 46.3, 35.7, 32.5, 29.2, 25.

[001695] Example 177: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2- (4,4-difluoropiperidin-1-yl) ethyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[001696] The compound was prepared in an analogous manner to Example 35 from 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra - hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide (Example 117) and isolated as a white powder.

[001697] 1H NMR (DMSOd6): 11.74 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.13 (1 H, dd, J = 11.3, 9.4 Hz), 3.71 (1 H, dd, J = 11.6, 7.8 Hz), 3 , 29 (1 H, dd, J = 15.6, 9.4 Hz), 2.88 (1 H, dd, J = 15.7, 7.9 Hz), 2.58-2.46 (8 H, m), 1.91 (4 H, m). 13

[001698] C NMR (DMSOd6): 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 154.9, 132.4, 132.4, 128.1, 124.4, 122.8, 121.2, 119, 118.9, 118.7, 118, 113.8, 113.7, 113.6, 113.6, 104, 1, 104, 103.9, 103.9, 54.9, 49.2, 49.2, 49.1, 48.5, 35.7, 33.5, 33.4, 33.2, 29, 2, 22.1.

[001699] Example 178: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2 - ((1,1-dioxidotetrahydro-2H-thiopyran-4-yl) amino) ethyl ) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[001700] The compound was prepared in an analogous manner to Example 35 from 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra - hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-

il) acetamide (Example 130) and isolated as a cream powder.

[001701] 1H NMR (DMSOd6): 11.74 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.13 (1 H, dd, J = 9.7, 11.1 Hz), 3.71 (1 H, dd, J = 11.4, 7.9 Hz), 3 , 27 (1 H, dd, J = 15.5, 9.2 Hz), 3.08 (2 H, m), 2.98 (2 H, m), 2.89 (1 H, dd, J = 15.6, 8.1 Hz), 2.73 (1 H, m), 2.68 (2 H, t, J = 7.2 Hz), 2.46 (2 H, t, J = 7 , 1 Hz), 2.01 (2 H, m), 1.83 (2 H, m). 13

[001702] C NMR (DMSOd6): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155, 132.5, 132, 4, 128.1, 118.9, 118.7, 118.6, 118.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103, 9, 54.9, 50.4, 48.4, 47.7, 44.8, 35.7, 29.1, 29, 29, 25.

[001703] Example 179: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2- (4- (methylsulfonyl) piperidin-1-yl) ethyl) -2,5,6, 7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[001704] The compound was prepared in an analogous manner to Example 35 from 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra - hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide (Example 126) and isolated as a white powder.

[001705] 1H NMR (DMSOd6): 11.74 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.13 (1 H, dd, J = 11.3, 9.4 Hz), 3.70 (1 H, dd, J = 11.7, 7.8 Hz), 3 , 28 (1 H, dd, J = 15.6, 9.4 Hz), 3.01 (1 H, tt, J = 3.6, 12.4 Hz), 3.0-2.94 (2 H, m), 2.90 (3 H, s), 2.89 (1 H, dd, J = 8.0, 15.4 Hz), 2.50 (4 H, m), 1.94 ( 4 H, m), 1.55 (2 H, m). 13

[001706] C NMR (DMSOd6): 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 154.9, 132.4, 132.4, 128.1, 118.9, 118.8, 118.7,

118.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 58.8, 55.7, 51.4, 51.3, 48.5, 37.4, 35.7, 29.2, 24.4, 24.4, 22.

[001707] Example 180: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- ((2,2,2-trifluoroethyl) amino) ethyl) -5,5a, 6, 6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001708] The compound was prepared in an analogous way to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- (2,2,2-trifluoroethyl) acetamide (Example 152) and isolated as a yellow solid.

[001709] 1H NMR (DMSOd6): 11.65 (1 H, s), 7.59 (1 H, dd, J = 6.7, 2.6 Hz), 7.55 (1 H, ddd, J = 8.7, 4.5, 2.5 Hz), 7.24 (1 H, dd, J = 10.2, 8.7 Hz), 4.06 (1 H, d, J = 11, 4 Hz), 3.77 (1 H, d, J = 12.0 Hz), 3.26 (2 H, m), 2.90 (1 H, dd, J = 8.4, 4.3 Hz ), 2.84 (2 H, m), 2.54 (2 H, m), 1.62 (1 H, dd, J = 8.3, 5.4 Hz), 1.16 (1 H, t, J = 4.8 Hz). 13

[001710] C NMR (DMSOd6): 161.8, 160.1, 155.8, 132.8, 132.8, 132.3, 132.2, 130.7, 129.5, 129.4, 129, 127.2, 125.3, 123.5, 118, 117.8, 117.5, 116.2, 116.2, 51.4, 49.3, 49.1, 48.9, 48, 7, 47.7, 32.2, 24.8, 22.3, 20.4.

[001711] Example 181: (S) -6- (3-bromo-2,6-difluorophenyl) -1- (2- (cyclobutylamino) ethyl) -2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazole-3-thione

[001712] The compound was prepared analogously to Example 35 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra - hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N-cyclobutylacetamide (Example 102) and isolated as a white powder.

[001713] 1H NMR (DMSOd6): 11.73 (1 H, m), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, t, J = 8.7 Hz), 4.13 (1 H, dd, J = 11.3, 9.4 Hz), 3.71 (1 H, dd, J = 11.6, 7.9 Hz), 3 , 26 (1 H, dd, J = 15.6, 9.4 Hz), 3.18 (1 H, quin, J = 7.5 Hz), 2.88 (1 H, dd, J = 15, 6, 8.1 Hz), 2.64 (2 H, t, J = 7.1 Hz), 2.45 (2 H, t, J = 7.0 Hz), 2.07 (2 H, m ), 1.75-1.45 (4 H, m). 13

[001714] C NMR (DMSOd6): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155, 132.5, 132, 4, 128.1, 118.8, 118.7, 118.6, 118, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 53.2, 48.4, 44.6, 35.7, 30, 29.1, 24.7, 14.5.

[001715] Example 182: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2 - ((2- (methylsulfonyl) ethyl) amino) ethyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2- c] imidazole-3-thione

[001716] The compound was prepared analogously to Example 35 from (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra - hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (2- (methylsulfonyl) ethyl) acetamide (Example 118) and isolated as a yellow powder.

[001717] 1H NMR (DMSOd6): 11.73 (1 H, br s), 7.73 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 9.5, 11.5 Hz), 3.71 (1 H, dd, J = 11.5, 8.1 Hz), 3.26 (1 H, dd, J = 15.5, 9.2 Hz), 3.20 (2 H, t, J = 6.7 Hz), 2.97 (3 H, s), 2, 91 (2 H, t, J = 6.7 Hz), 2.91 (1 H, m), 2.70 (2 H, t, J = 7.0 Hz), 2.47 (2 H, t , J = 7.0 Hz). 13

[001718] C NMR (DMSOd6): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155, 132.5, 132, 4, 128.2, 118.7, 118.6, 118.5, 118, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 53.6, 48.4, 47, 42.4, 41.4, 35.7, 29, 24.7.

[001719] Example 183: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2 - ((2-hydroxyethyl) (methyl) amino) ethyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2- c] imidazole-3-thione

[001720] The compound was prepared in an analogous way to Example 35 from (R) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra - hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (2-hydroxyethyl) -N-methylacetamide (Example 131) and isolated as a brown powder.

[001721] 1H NMR (DMSOd6): 11.72 (1 H, s), 7.72 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.41 (1 H, t, br, J = 5.5 Hz), 4.13 (1 H, dd, J = 11.2, 9.5 Hz), 3.70 (1 H, dd, J = 11.6, 8.1 Hz), 3.44 (2 H, q, J = 6.1 Hz), 3.27 (1 H, dd, J = 15.5, 9.3 Hz), 2.88 (1 H, dd, J = 15.6, 8.3 Hz), 2.52 (2 H, m), 2.48 (2 H, t, J = 7, 1 Hz), 2.41 (2 H, t, J = 6.2 Hz), 2.18

(3 H, s). 13

[001722] C NMR (DMSOd6): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 154.9, 132.5, 132.4, 127.9, 118.8, 118.6, 118.5, 118.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 58.9, 58.8, 55.8, 48.4, 42, 35.7, 29.1, 22.1.

[001723] Example 184: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2 - ((((R) -1- cyclohexylethyl) amino) ethyl) -2,5, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[001724] The compound was prepared in an analogous manner to Example 35 from 2 - ((R) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra - hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -1-cyclohexylethyl) acetamide (Example 127) and isolated as a cream powder.

[001725] 1H NMR (DMSOd6): 11.84 (1 H, br), 7.73 (1 H, m), 7.17 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.13 (1 H, dd, J = 11.2, 9.4 Hz), 3.71 (1 H, dd, J = 11.6, 7.8 Hz), 3 , 28 (1 H, dd, J = 15.7, 9.5 Hz), 2.88 (1 H, dd, J = 15.6, 8.2 Hz), 2.83, 2.71 (2 H, 2 br s), 2.50 (3 H, m), 1.68 (2 H, br d, J = 12.6 Hz), 1.60 (3 H, m), 1.38-1 , 0 (5 H, m), 0.94 (4 H, m). 13

[001726] C NMR (DMSOd6): 160.8, 160.7, 159.1, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 128.2, 118.8, 118.7, 118.6, 113.8, 113.6, 104.1, 103.9, 57, 48.4, 44.8, 41.8, 35.7, 29.2, 29.2, 27.1, 26.2, 26.1, 25.9, 24.6, 15.7.

[001727] Example 185: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (pyrrolidin-1-yl) ethyl) -5.5a, 6.6a-tetrahydrochloride - hydrocycloprop [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001728] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (pyrrolidin-1-yl) ethan-1-one (Example 70) and isolated as a beige solid .

[001729] 1H NMR (DMSOd6): 11.80 (1 H, br s), 9.60 (1 H, br s), 7.59 (1 H, dd, J = 6.7, 2.5 Hz), 7.56 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.25 (1 H, dd, J = 10.0, 8.8 Hz), 4 , 08 (1 H, d, J = 12.0 Hz), 3.80 (1 H, d, J = 12.2 Hz), 3.39-3.05 (6 H, m), 2.97 (1 H, dd, J = 8.4, 4.3 Hz), 2.83 (2 H, m), 1.91 (4 H, br s), 1.67 (1 H, dd, J = 8.2, 5.3 Hz), 1.19 (1 H, t, J = 4.7 Hz). 13

[001730] C NMR (DMSOd6): 161.8, 160.1, 156.5, 132.9, 132.9, 132.4, 132.3, 131.7, 129.2, 129.1, 118, 117.9, 116.2, 116.2, 114.6, 53.4, 52.4, 51.5, 32.4, 22.7, 22.1, 21.3, 20.3.

[001731] Example 186: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) hydrochloride -1- (2 - ((cyclopropylmethyl) amino) ethyl) -5.5a, 6.6a-tetra- hydrocycloprop [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001732] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- (cyclopropylmethyl) acetamide (Example 143) and isolated as a beige solid.

[001733] 1H NMR (DMSOd6): 11.79 (1 H, s br), 8.39 (2 H, s br), 7.59 (1 H, dd, J = 6.7, 2.5 Hz), 7.56 (1 H, ddd, J = 8.6, 4.4, 2.6 Hz), 7.25 (1 H, dd, J = 9.9, 8.9 Hz), 4 , 08 (1 H, br d, J = 12.0 Hz), 3.79 (1 H, d, J = 12.0 Hz), 3.17 (2 H, t, J = 7.3 Hz) , 2.93 (1 H, dd, J = 8.2, 4.3 Hz), 2.87-2.73 (4 H, m), 1.67 (1 H, dd, J = 8.1 , 5.4 Hz), 1.20 (1 H, t, J = 4.8 Hz), 1.02 (1 H, m), 0.58 (2 H, m), 0.34 (2 H , m). 13

[001734] C NMR (DMSOd6): 161.8, 160.1, 156.5, 133, 132.9, 132.4, 132.3, 131.7, 129.3, 129.2, 118, 117.9, 116.2, 116.2, 114.7, 51.5, 51.4, 44.8, 32.4, 22.1, 21.3, 20.3, 7.3, 3, 9, 3.8.

[001735] Example 187: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (cyclopropylamino) ethyl) -5.5a, 6.6a-tetrahydrocyclopropane [3 , 4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001736] The compound was prepared in an analogous way to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N-cyclopropylacetamide (Example 154) and isolated as a beige solid.

[001737] 1H NMR (DMSOd6): 11.76 (1 H, br s), 7.59 (1 H, dd, J = 6.6, 2.5 Hz), 7.56 (1 H, ddd , J = 8.6, 4.5, 2.6 Hz), 7.25 (1 H, dd, J = 10.0, 8.9 Hz), 4.07 (1 H, d, J = 12 , 0 Hz), 3.78 (1 H, d, J = 12.0 Hz), 3.14 (2 H,

m), 2.93 (1 H, dd, J = 8.3, 4.2 Hz), 2.73 (2 H, m), 2.52 (1 H, m), 1.65 (1 H , dd, J = 8.2, 5.3 Hz), 1.19 (1 H, t, J = 4.8 Hz), 0.70-0.57 (4 H, m). 13

[001738] C NMR (DMSOd6): 161.8, 160.1, 156.3, 132.9, 132.9, 132.3, 132.3, 131.4, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 115.4, 51.5, 46.2, 32.4, 29.5, 22.2, 22.2, 20.4, 4.1, 4.

[001739] Example 188: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (cyclobutylamino) ethyl) -5.5a, 6.6a-tetrahydrocyclopropyl fluorohydrate [3 , 4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001740] The compound was prepared in an analogous manner to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N-cyclobutylacetamide (Example 153) and isolated as a beige solid.

[001741] 1H NMR (DMSOd6): 11.80 (1 H, s br), 8.44 (1 H, s br), 7.59 (1 H, dd, J = 6.7, 2.5 Hz), 7.56 (1 H, ddd, J = 8.7, 4.4, 2.6 Hz), 7.25 (1 H, dd, J = 10.0, 8.9 Hz), 4 , 07 (1 H, d, J = 12.0 Hz), 3.78 (1 H, d, J = 12.0 Hz), 3.65 (1 H, quin, J = 8.0 Hz), 3.02 (2 H, t, J = 7.2 Hz), 2.94 (1 H, dd, J = 8.3, 4.2 Hz), 2.74 (2 H, m), 2, 18 (2 H, m), 2.08 (2 H, m), 1.77 (2 H, m), 1.66 (1 H, dd, J = 8.2, 5.3 Hz), 1 , 20 (1 H, t, J = 4.7 Hz).

[001742] 13C NMR (DMSOd6): 161.8, 160.1, 156.5, 133, 133, 132.4, 132.3, 131.8, 129.3, 129.2, 118, 117, 9, 116.2, 116.2, 114.6, 51.6, 51.6, 51.1, 42.8, 32.4, 26.4, 22.1, 21.6, 20.3, 14.5.

[001743] Example 189: (5aS, 6aR) -1- (2- (benzylamino) ethyl) -5a- (5-chloro-2-fluorophenyl) -5.5a, 6.6a-tetrahydrocyclopropyl fluorohydrate [3 , 4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001744] The compound was prepared in an analogous manner to Example 35 from N-benzyl-2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetamide (Example 156) and isolated as a beige solid.

[001745] 1H NMR (DMSOd6): 11.79 (1 H, br s), 8.28 (2 H, br m), 7.50-7.41 (6 H, m), 7.39 ( 1 H, m), 7.31 (1 H, dd, J = 9.0, 9.9 Hz), 4.10 (2 H, s), 4.08 (1 H, d, J = 12, 3 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.12 (2 H, t, J = 6.8 Hz), 2.90 (1 H, dd, J = 8 , 4, 4.3 Hz), 2.78 (2 H, m), 1.66 (1 H, dd, J = 8.2, 5.3 Hz), 1.19 (1 H, t, J = 4.7 Hz). 13

[001746] C NMR (DMSOd6): 161.2, 159.6, 156.4, 133.6, 131.5, 130.1, 130.1, 129.5, 129.4, 129.3, 128.9, 128.8, 128.6, 128.6, 128.3, 117.6, 117.4, 115.1, 51.5, 50.6, 45.5, 32.4, 22, 1, 21.8, 20.4.

[001747] Example 190: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (cyclopentyl (methyl) amino) ethyl) -5.5a, 6.6a-tetra fluorohydrate - hydrocycloprop [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N-cyclopentyl-N-methylacetamide (Example 155) and isolated as a beige solid.

[001749] 1H NMR (DMSOd6): 11.81 (1 H, br s), 9.42 (1 H, m), 7.63- 7.49 (2 H, m), 7.25 (1 H, t, J = 9.3 Hz), 4.08 (1 H, d, J = 12.0 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.29 ( 2 H, m), 2.95 (2 H, dd, J = 7.8, 3.9 Hz), 2.78 (4 H, br m), 1.97 (2 H, br m), 1 , 78-1.37 (7 H, m), 1.17 (1 H, m), 1 H (br). 13

[001750] C NMR (DMSOd6): 161.7, 160.1, 156.4, 132.9, 132.8, 132.3, 132.3, 131.4, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 66.1, 52.6, 51.5, 37.8, 32.4, 27.9, 23.7, 22.2, 20.3, 19.6.

[001751] Example 191: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2-morpholinoethyl) -5.5a, 6.6a-tetrahydrocyclopropane [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001752] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- morpholinoethane-1-one (Example 157) and isolated as an off-white solid.

[001753] 1H NMR (DMSOd6): 11.85 (1 H, br s), 11.05 (1 H, br s), 7.64-7.52 (2 H, m), 7.25 ( 1 H, br t, J = 9.3 Hz), 4.08 (1 H, d, J = 11.9 Hz), 3.98 (2 H, br m), 3.79 (3 H, m ), 3.44 (2 H, m), 3.35 (2 H, m), 3.10 (2 H, br s), 2.97 (3 H, br s), 1.67 (1 H , m), 1.19 (1 H, br s).

[001754] C NMR (DMSOd6): 161.8, 160.1, 156.6, 132.9, 132.4, 132.3, 131.5, 129.2, 129.1, 118, 117, 8, 116.2, 114.3, 63.1, 53.9, 51.5, 51.2, 50.9, 32.4, 22.1, 20.4, 18.7.

[001755] Example 192: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (pyridin-2-ylamino) ethyl) -5.5a, 6.6a-tetra fluorohydrate - hydrocycloprop [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001756] The compound was prepared in an analogous manner to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- (pyridin-2-yl) acetamide (Example 170) and isolated as a dark beg solid.

[001757] 1H NMR (DMSOd6): 11.75 (1 H, s), 7.95 (1 H, dd, J = 5.4, 1.5 Hz), 7.64-7.43 (3 H, m), 7.23 (1 H, t, J = 9.8 Hz), 6.66 (1 H, br s), 6.58 (1 H, br s), 4.05 (1 H , d, J = 11.9 Hz), 3.76 (1 H, d, J = 12.1 Hz), 3.50 (2 H, m), 2.73 (1 H, dd, J = 8 , 1, 4.2 Hz), 2.69 (2 H, t, J = 6.9 Hz), 1.54 (1 H, dd, J = 8.2, 5.3 Hz), 1.11 (1 H, t, J = 4.8 Hz). 13

[001758] C NMR (DMSOd6): 161.7, 160.1, 157.3, 155.9, 145.6, 137.9, 132.8, 132.8, 132.2, 132.2, 131.1, 129.4, 129.3, 118, 117.8, 117.1, 116.1, 111.6, 109.2, 51.4, 39.4, 32.2, 24, 22, 4, 20.3.

[001759] Example 193: (S) -6- (3-chloro-2,6-difluorophenyl) hydrochloride -1- (2- (methylamino) ethyl) -2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazole-3-thione

[001760] The compound was prepared analogously to Example 35 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) -N-methylacetamide and isolated as a white solid.

[001761] 1H NMR (DMSOd6): 11.89 (1 H, s), 8.93 (2 H, m), 7.63 (1 H, m), 7.23 (1 H, m), 4.44 (1 H, quin, J = 8.8 Hz), 4.14 (1 H, dd, J = 11.3, 9.4 Hz), 3.75 (1 H, dd, J = 11 , 5, 8.4 Hz), 3.31 (1 H, dd, J = 9.1, 15.6 Hz), 3.09 (2 H, br s), 2.94 (1 H, dd, J = 15.6, 8.7 Hz), 2.76 (2 H, m), 2.52 (3 H, br s). 13

[001762] C NMR (DMSOd6): 160.2, 160.1, 158.5, 158.5, 156.6, 156.6, 155.9, 155, 154.9, 129.8, 129, 7, 129.5, 118.4, 118.2, 118.1, 116.1, 116.1, 116, 115.9, 114.7, 113.3, 113.2, 113.1, 113, 1, 48.3, 46.4, 35.8, 32.3, 29, 21.

[001763] Example 194: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -1- (2- (piperidin-1-yl) ethyl) -5.5a, 6.6a-tetra fluorohydrate - hydrocycloprop [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[001764] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6 , 6a- hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (piperidin-1-yl) ethan-1-one (Example 158) and isolated as a beige solid .

[001765] 1H NMR (DMSOd6): 11.80 (1 H, br s), 9.08 (2 H, br s), 7.47 (1 H, dd, J = 6.5, 2.6 Hz), 7.44 (1 H, ddd, J = 8.6, 4.3, 2.8 Hz), 7.31 (1 H, dd, J = 9.1, 9.9 Hz), 4 , 08 (1 H, d, J = 11.9 Hz), 3.80 (1 H, d, J = 12.0 Hz), 3.50-2.63 (8 H, m), 2.94 (1 H, dd, J = 8.3, 4.2 Hz), 2.0-1.25 (6 H, m), 1.68 (1 H, dd, J = 8.3, 5.4 Hz), 1.18 (1 H, t, J = 4.5 Hz). 13

[001766] C NMR (DMSOd6): 161.2, 159.6, 156.4, 131.4, 130, 129.4, 129.3, 128.8, 128.7, 128.3, 117, 6, 117.4, 114.7, 54.4, 52.6, 51.5, 32.4, 23, 22.1, 21.7, 20.4, 19.6.

[001767] Example 195: (S) -6- (3-bromo-2,6-difluorophenyl) -1- (2-morpholinoethyl) -2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazole-3-thione

[001768] The compound was prepared analogously to Example 35 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra - hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1-morpholinoethane-1-one (Example 140) and isolated as a beige powder.

[001769] 1H NMR (DMSOd6): 11.73 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.7 Hz), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.13 (1 H, dd, J = 11.5, 9.2 Hz), 3.70 (1 H, dd, J = 11.6, 7.8 Hz), 3.53 (4 H, br t, J = 4.5 Hz), 3.28 (1 H, dd, J = 15.6, 9.4 Hz), 2.89 (1 H, dd, J = 15.6, 8.0 Hz), 2.51 (2 H, m) 2.46 (2 H, m), 2.34 (4 H, br s). 13

[001770] C NMR (DMSOd6): 160.8, 160.7, 159.1, 159.1, 157.6, 157.5, 155.9, 155.9, 154.8, 132.4, 132.4, 128.1, 119, 118.8, 118.7,

118.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 66.2, 56.3, 53, 48.5, 35, 7, 29.3, 21.5.

[001771] Example 196: (S) -6- (3-chloro-2,6-difluorophenyl) -1- (2-morpholinoethyl) -2,5,6,7-tetrahydro-3H-pyrrole hydrochloride [ 1,2-c] imidazole-3-thione

[001772] The compound was prepared analogously to Example 35 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) -1-morpholinoetan-1-one and isolated as a white solid.

[001773] 1H NMR (DMSOd6): 11.93 (1 H, s), 11.01 (1 H, br s), 7.63 (1 Hm), 7.23 (1 H, m), 4 , 47 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, dd, J = 11.4, 9.2 Hz), 3.96 (2 H, br d, J = 12 , 2 Hz), 3.76 (3 H, m), 3.40 (2 H, br d, J = 12.0 Hz), 3.31 (2 H, m), 3.05 (2 H, m), 2.94 (1 H, br dd, J = 15.8, 8.1 Hz), 2.89 (2 H, br t, J = 7.5 Hz). 13

[001774] C NMR (DMSOd6): 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.8, 154.9, 154.9, 129.8, 129.7, 129.1, 118.7, 118.6, 118.5, 116.1, 116.1, 116, 115.9, 114.7, 113.3, 113.2, 113.1, 113.1, 63.1, 53.8, 51.1, 48.5, 35.7, 29.1, 18.8.

[001775] Example 197: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -1- (2- (pyridin-3-ylamino) ethyl) -5.5a, 6.6a-tetrahydrocyclopropa [3.4] pyrrole [1,2- c] imidazole-3 (2H) -thione

[001776] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6 , 6a hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- (pyridin-3-yl) acetamide (Example 171) and isolated as a beige solid.

[001777] 1H NMR (DMSOd6): 11.78 (1 H, br s), 8.00 (1 H, d, J = 2.8 Hz), 7.75 (1 H, dd, J = 4 , 5, 1.2 Hz), 7.46 (1 H, dd, J = 6.5, 2.6 Hz), 7.42 (1 H, ddd, J = 8.7, 4.3, 2 , 8 Hz), 7.29 (1 H, dd, J = 9.0, 9.9, Hz), 7.07 (1 H, dd, J = 8.3, 4.6 Hz), 6, 96 (1 H, ddd, J = 1.2, 2.7, 8.3 Hz), 5.93 (1 H, t, J = 5.9 Hz), 4.06 (1 H, d, J = 11.9 Hz), 3.77 (1 H, d, J = 12.2 Hz), 3.30 (2 H, m), 2.81 (1 H, dd, J = 8.2, 4 , 3 Hz), 2.66 (2 H, m), 1.56 (1 H, dd, J = 8.2, 5.3 Hz), 1.14 (1 H, t, J = 4.8 Hz). 13

[001778] C NMR (DMSOd6): 161.2, 159.6, 155.9, 144.4, 135.3, 131.1, 130, 129.9, 129.3, 129.2, 129, 128.9, 128.3, 128.2, 123.6, 117.5, 117.4, 117.4, 117, 51.4, 51.4, 41.2, 32.3, 23.9, 22.3, 20.3.

[001779] Example 198: (R) -1- (2- (pyrrolidin-1-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydrochloride -hydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[001780] The compound was prepared in an analogous manner to Example 35 from (R) -1- (pyrrolidin-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo - 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one (Example 104) and isolated as a light yellow solid.

[001781] 1H NMR (DMSOd6): 11.92 (1 H, s), 10.90 (1 H, br s), 7.87 (1 H, m), 4.51 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.5, 9.2 Hz), 3.78 (1 H, dd, J = 11.6, 7.8 Hz), 3.47 (2 H, m), 3.37 (1 H, m), 3.32 (2 H, m), 2.98 (3 H, m), 2.85 (2 H, br t, J = 7.8 Hz), 1.98 (2 H, m), 1.86 (2 H, m). 13

[001782] C NMR (DMSOd6): 155.9, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.7, 144.7, 144.7, 144.6, 144, 6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 129, 120.4, 120.3, 120.2, 114, 9, 105.9, 105.8, 105.6, 53, 52, 48.4, 35.8, 29, 22.7, 20.8.

[001783] Example 199: (R) -1- (2-morpholinoethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole hydrochloride [ 1,2-c] imidazole-3-thione

[001784] The compound was prepared analogously to Example 35 from (R) -1-morpholino-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a light cream powder.

[001785] 1H NMR (DMSOd6): 11.95 (1 H, s), 11.05 (1 H, br s), 7.88 (1 H, m), 4.51 (1 H, quin, J = 8.4 Hz), 4.17 (1 H, br dd, J = 11.4, 9.4 Hz), 3.96 (2 H, br d, J = 12.2 Hz), 3, 78 (3 H, m), 3.41 (2 H, m), 3.36 (1 H, m), 3.30 (2 H, m), 3.06 (2 H, m), 2, 98 (1 H, br dd, J = 15.7, 7.9 Hz), 2.89 (2

H, m). 13

[001786] C NMR (DMSOd6): 155.9, 146.4, 146.3, 146.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143, 6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.8, 106, 105.8, 105.6, 63.1, 53.8, 51.1, 48, 4, 35.8, 29, 18.8.

[001787] Example 200: 2 - ((6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [1,2-c] (R) -diethyl imidazol-1-yl) methyl) malonate

[001788] Step 1: tert-Butyl (4R) -2- (2-diazoacetyl) -4- (2,3,5,6- tetrafluorophenyl) pyrrolidine-1-carboxylate

[001789] To a solution of (4R) -1- (tert-butoxycarbonyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-2-carboxylic acid (2 g, 5.51 mmol) and N- ethyl-N-isopropylpropan-2-amine (DIPEA) (1.68 mL, 9.63 mmol) in dry tetrahydrofuran (20 mL) ethyl chloroformate (0.793 mL, 8.26 mmol) was added at 0-5 ° C. The mixture was stirred for 4 h in the cold, and then diluted with acetonitrile (10 ml) followed by addition of 2 M (diazomethyl) trimethylsilane (5.51 ml 11.01 mmol) in diethyl ether. Stirring was continued for an additional 3 h at 0-5 ° C and the mixture was allowed to warm naturally overnight with stirring under N2. After that, the solvents were removed in vacuo and the residue was purified by column chromatography on a mixture of petroleum ether - ethyl acetate to give 2- (2-diazoacetyl) -4- (2,3,5,6-tetrafluorophenyl ) (4R) -tert-butyl pyrrolidine-1-carboxylate as a yellow oil. Yield: 1.99 g, 93%.

[001790] Step 2: tert-Butyl (4R) -2- (2-bromoacetyl) -4- (2,3,5,6- tetrafluorophenyl) pyrrolidine-1-carboxylate

[001791] To a solution of 2- (2-diazoacetyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate (4R) -tert-butyl (1.98 g, 5.11 mmol) in diethyl ether (15 mL) 48% HBr (0.61 mL, 5.37 mmol) was added at 0-5 ° C with stirring. After 5 min, the mixture was diluted with ethyl acetate (20 ml) and then washed with sodium bicarbonate solution. The organic phase was dried (MgSO4), filtered, evaporated to dryness to give 2- (2R) -terc- 2- (2-bromoacetyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate butyl as a yellowish oil. Yield: 1.83 g, 81%.

[001792] Step 3: 2- (2 - ((4R) -1- (tert-butoxycarbonyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidin-2-yl) -2-oxoethyl) malonate diethyl

[001793] To a solution of diethyl malonate (0.83 mL, 5.45 mmol) in N, N-dimethylformamide (7 mL) was added sodium hydride (60% in mineral oil) (0.174 g, 4.36 mmol) with ice cooling and the solution was stirred for 30 min. After that, (4R) - tert-butyl 2- (2-bromoacetyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate (1.6 g, 3.63 mmol) in dry tetrahydrofuran (3.50 ml) to the above reaction mixture with ice cooling and the mixture was stirred in the cold for 30 min. The reaction was then diluted with a mixture of ethyl acetate - petroleum ether (2: 1), washed with NaHSO4 solution (40 mL), dried over MgSO4, filtered and evaporated to dryness. Chromatography on a mixture of ethyl acetate - petroleum ether gave the title product as a white powder. Yield: 1.15 g, 60%.

[001794] Step 4: 2- (2-oxo-2 - ((4R) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidin-2-yl) ethyl) diethyl malonate hydrochloride

[001795] 2- (2 - ((4R) -1- (Terc-butoxycarbonyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidin-2-yl) -2-oxoethyl) diethyl malonate (1 , 3 g, 2.502 mmol) was dissolved in 4 M HCl (9.38 mL, 37.5 mmol) in dioxane and the solution was stirred for 2 h. After that, the mixture was diluted with diethyl ether (about 150 ml). The resulting crystals were collected, washed with diethyl ether and dried under vacuum at 50 ° C to give 2- (2-oxo-2 - ((4R) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidin hydrochloride -2-yl) ethyl) diethyl malonate as a white powder. Yield: 1.02 g, 89%.

[001796] Step 5: (R) -2 - ((6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazol-1-yl) methyl) diethyl malonate

[001797] A hydrochloride mixture of diethyl 2- (2-oxo-2 - ((4R) -4- (2,3,5,6- tetrafluorophenyl) pyrrolidin-2-yl) ethyl) malonate (1.01 g,

2.216 mmol), potassium isothiocyanate (0.237 g, 2.437 mmol) and HCl cc (0.092 mL, 1.108 mmol) in abs ethanol. (22 mL) was stirred at reflux for 30 min. The suspension was then cooled to room temperature, evaporated to dryness and the residue was partitioned between dichloromethane and water. The organic phase was dried (MgSO4), filtered and evaporated to dryness to give the title product as a yellow powder. Yield: 0.94 g, 92% yield.

[001798] 1H NMR (DMSOd6): 1.80 (1 H, s), 7.85 (1 H, m), 4.47 (1 H, quin, J = 8.4 Hz), 4.20 -4.05 (5 H, m), 3.81 (1 H, t, J = 8.0 Hz), 3.74 (1 H, dd, J = 11.8, 7.4 Hz), 3 , 28 (1 H, dd, J = 15.8, 9.4 Hz), 2.93-2.80 (3 H, m), 1.14 (6 H, q, J = 7.3 Hz) . 13

[001799] C NMR (DMSOd6): 168, 167.9, 155.7, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145, 3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.6, 143.6, 143.6, 143.5, 143.5, 143.5, 129.1, 120.6, 120.5, 120.4, 115.6, 105.9, 105.7, 105, 6, 61.3, 61.2, 50.1, 48.5, 35.7, 29, 23.5, 13.8, 13.8.

[001800] Example 201: (R) -2 - ((6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1 , 2-c] imidazol-1-yl) methyl) malonic

[001801] To a solution of 2 - ((6- (2,3,5,6-tetrafluorophenyl) -3-thioxo- 3,5,6,7-tetrahydro-2H-pyrrole [1,2-c ] (R) - diethyl imidazol-1-yl) methyl) malonate (Example 200) (0.9 g, 1.955 mmol) in methanol (20 mL) 1 M sodium hydroxide solution (11.72 mL, 11.72 mmol) and the mixture was stirred at room temperature overnight. After that, methanol was removed in vacuo, the residue was diluted with water (20 ml) and then acidified to pH = 1 by adding 2 M HCl solution with ice cooling. The mixture was then extracted with 50 ml of a mixture of dichloromethane - isopropanol (9: 1), the organic phase was dried over MgSO4, filtered and evaporated to 5 ml in volume. The resulting precipitate was collected by filtration, washed with petroleum ether and dried under vacuum at 50 ° C to give (R) -2 - ((6- (2,3,5,6-tetrafluorophenyl) -3-thioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) methyl) malonic as a yellow powder. Yield: 0.74 g, 94%.

[001802] 1H NMR (DMSOd6): 12.93 (1 H, br s), 11.79 (1 H, s), 7.85 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.6, 9.2 Hz), 3.75 (1 H, dd, J = 8.0, 11.5 Hz), 3.56 (1 H, t, J = 8.0 Hz), 3.26 (1 H, dd, J = 15.8, 9.3 Hz), 2.89 (1 H, dd, J = 15 , 8, 8.2 Hz), 2.80 (2 H, dd, J = 7.9, 2.9 Hz). 13

[001803] C NMR (DMSOd6): 169.8, 169.8, 155.5, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144, 6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 143.6, 128.8, 120.3, 120.2, 120.1, 116.4, 105.9, 105.8, 105.6, 50.6, 48.3, 35.7, 29, 23.7.

[001804] Example 202: (R) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1, 2-c] imidazol-1-yl) propanoic

[001805] To a solution of (R) -2 - ((6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [ 1,2-c] imidazol-1-yl) methyl) malonic (0.1 g, 0.247 mmol) in formic acid (0.237 mL, 6.18 mmol) was added dropwise triethylamine (0.345 mL, 2.473 mmol) ) with stirring (exothermic reaction) and then the resulting solution was stirred at 115 ° C for 1 h. After that, the mixture was diluted with water to 4 ml, the resulting oil mixture treated with 2 M HCl (0.5 ml) and then aged for 30 min. The resulting solid was collected, washed with water and dried under vacuum at 50 ° C to give (R) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6 acid , 7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) propanoic as a beige powder. Yield: 0.051 g, 57%.

[001806] 1H NMR (DMSOd6): 12.22 (1 H, br), 11.78 (1 H, s), 7.85 (1 H, m), 4.47 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.7, 9.2 Hz), 3.75 (1 H, dd, J = 11.7, 7.8 Hz), 3 , 30 (1 H, br dd, J = 15.7, 9.4 Hz), 2.92 (1 H, dd, J = 15.7, 8.1 Hz), 2.63-2.54 ( 2 H, m), 2.5 (2 H, m). 13

[001807] C NMR (DMSOd6): 173.4, 155.2, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143, 6, 143.6, 143.6, 143.6, 128, 127.7, 120.4, 120.3, 120.2, 118.7, 105.9, 105.7, 105.6, 48, 3, 35.8, 32.2, 29, 19.7.

[001808] Example 203: (R) -N- (cyclopropylmethyl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazol-1-yl) propanamide

[001809] The compound was prepared analogously to Example 32 from (R) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7- acid tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanoic (Example 202) and isolated as an off-white powder.

[001810] 1H NMR (DMSOd6): 11.72 (1 H, br s), 7.90 (1 H, br t, J = 5.5 Hz), 7.86 (1 H, m), 4 , 46 (1 H, quin, J = 8.5 Hz), 4.14 (1 H, dd, J =

11.5, 9.2 Hz), 3.74 (1 H, dd, J = 11.7, 7.8 Hz), 3.29 (1 H, dd, J = 15.7, 9.2 Hz ), 2.91 (1 H, m), 2.89 (2 H, br t, J = 6.2 Hz), 2.57 (2 H, m), 2.34 (2 H, t, J = 7.4 Hz), 0.83 (1 H, m), 0.35 (2 H, m), 0.09 (2 H, m). 13

[001811] C NMR (DMSOd6): 170.5, 155, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 146.2, 145.3, 145, 3, 145.3, 145.2, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 143.5, 127.5, 120.5, 120.4, 120.3, 119, 1, 105.9, 105.7, 105.5, 48.2, 42.8, 35.8, 33.4, 29.1, 20, 10.7, 3.1.

[001812] Example 204: (R) -1- (pyrrolidin-1-yl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one

[001813] The compound was prepared analogously to Example 32 from (R) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanoic (Example 202) and isolated as an off-white powder.

[001814] 1H NMR (DMSOd6): 11.73 (1 H, br s), 7.85 (1 H, t, J = 9.0 Hz), 4.46 (1 H, quin, J = 8 , 6 Hz), 4.15 (1 H, dd, J = 11.5, 9.2 Hz), 3.74 (1 H, dd, J = 11.7, 7.8 Hz), 3.36 (2 H, t, J = 6.8 Hz), 3.30 (1 H, br dd, J = 15.7, 9.4 Hz), 3.25 (2 H, t, J = 6.9 Hz), 2.93 (1 H, dd, J = 15.7, 8.1 Hz), 2.56 (2 H, m), 2.51 (2 H, m), 1.84 (2 H , m), 1.74 (2 H, m).

[001815] 13C NMR (DMSOd6): 169, 155, 146.4, 146.3, 146.3, 145.3, 145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 127.6, 120.5, 120.4, 120.3,

119.2, 105.8, 105.7, 105.5, 48.2, 45.7, 45.3, 35.8, 32.2, 28.9, 25.5, 23.9, 19, 5.

[001816] Example 205: (R) -1-morpholino-3- (6- (2,3,5,6-tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) propan-1-one

[001817] The compound was prepared analogously to Example 32 from (R) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7- acid tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanoic (Example 202) and isolated as a beige powder.

[001818] 1H NMR (DMSOd6): 11.73 (1 H, br s), 7.86 (1 H, m), 4.47 (1 H, quin, J = 8.6 Hz), 4, 15 (1 H, dd, J = 11.4, 9.3 Hz), 3.75 (1 H, dd, J = 11.6, 7.9 Hz), 3.52 (4 H, dt, J = 13.2, 4.7 Hz), 3.42 (4 H, m), 3.31 (1 H, dd, J = 9.3, 15.7 Hz), 2.94 (1 H, dd , J = 15.6, 8.1 Hz), 2.58 (4 H, m). 13

[001819] C NMR (DMSOd6): 169.6, 155.1, 146.4, 146.3, 146.2, 145.3, 145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 127.6, 120.4, 120.3, 120.2, 119.1, 105.9, 105.7, 105.5, 66.1, 66.1, 48, 2, 45.2, 41.5, 35.8, 30.5, 28.9, 19.8.

[001820] Example 206: (R) -1- (4,4-difluoropiperidin-1-yl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one

[001821] The compound was prepared analogously to Example 32 from (R) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7- acid tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanoic (Example 202) and isolated as a light yellow powder.

[001822] 1H NMR (DMSOd6): 11.74 (1 H, s), 7.86 (1 H, m), 4.47 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.5, 9.3 Hz), 3.75 (1 H, dd, J = 11.6, 7.9 Hz), 3.54 (4 H, m), 3 , 31 (1 H, m), 2.94 (1 H, dd, J = 15.7, 8.2 Hz), 2.66 (2 H, m), 2.57 (2 H, m), 1.98 (2 H, m), 1.88 (2 H, m). 13

[001823] C NMR (DMSOd6): 169.5, 155.1, 146.4, 146.3, 146.2, 145.3, 145.2, 144.8, 144.7, 143.7, 143.6, 127.6, 124.3, 122.7, 121.1, 120.4, 120.3, 120.2, 119, 105.9, 105.7, 105.6, 48.2, 41.6, 41.5, 41.5, 38.1, 38, 38, 35.8, 34, 33.8, 33.7, 33.3, 33.2, 33, 30.5, 28, 9, 19.9.

[001824] Example 207: (R) -1- (piperidin-1-yl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one

[001825] The compound was prepared in an analogous manner to Example 32 from (R) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7- acid tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanoic (Example 202) and isolated as a beige powder.

[001826] 1H NMR (DMSOd6): 11.72 (1 H, br s), 7.86 (1 H, m), 4.46 (1 H, quin, J = 8.6 Hz), 4, 15 (1 H, dd, J = 11.6, 9.2 Hz), 3.75 (1 H, dd, J = 11.7, 7.8 Hz), 3.37 (4 H, m), 3.30 (1 H, dd, J = 9.3, 11.8 Hz), 2.93 (1 H, dd, J = 15.6, 8.1 Hz), 2.57 (4 H, m ), 1.55 (2 H, m), 1.45 (2 H, m), 1.38 (2 H, m). 13

[001827] C NMR (DMSOd6): 168.9, 155, 146.4, 146.3, 146.2, 145.3, 145.2, 145.2, 144.8, 144.7, 144, 6, 143.6, 143.6, 127.6, 120.4, 120.3, 120.2, 119.2, 105.8, 105.7, 105.5, 48.2, 45.7, 41.9, 35.8, 30.7, 28.9, 26, 25.3, 24, 20.

[001828] Example 208: (R) -1- (4-methylpiperidin-1-yl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one

[001829] The compound was prepared in an analogous manner to Example 32 from (R) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanoic (Example 202) and isolated as a beige powder.

[001830] 1H NMR (DMSOd6): 11.73 (1 H, s), 7.86 (1 H, m), 4.46 (1 H, quin, J = 8.6 Hz), 4.32 (1 H, br d, J = 13.2 Hz), 4.14 (1 H, m), 3.81 (1 H, br d, J = 13.5 Hz), 3.74 (1 H, dd, J = 11.7, 8.0 Hz), 3.30 (1 H, m), 2.92

(2 H, br dd, J = 15.1, 8.8 Hz), 2.56 (4 H, m), 2.47 (1 H, m), 1.57 (3 H, m), 0 , 95 (1 H, m), 0.87 (4 H, m). 13

[001831] C NMR (DMSOd6): 168.9, 155.1, 146.4, 146.3, 146.2, 145.3, 145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 127.5, 127.5, 120.4, 120.4, 120.3, 120.3, 120.2, 120.2, 119.2, 119.2, 105, 9, 105.7, 105.6, 48.2, 45, 44.9, 41.3, 35.8, 34.2, 33.5, 30.7, 30.6, 30.3, 29, 29, 21.6, 20.

[001832] Example 209: (R) -1- (morpholinomethyl) -6- (2,3,5,6-tetrafluorophenyl) -6,7-dihydro-2H-pyrrole hydrochloride [1,2-c] imidazole-3 (5H) -thione

[001833] Step 1: tert-butyl (4R) -2- (2-morpholinoacetyl) -4- (2,3,5,6- tetrafluorophenyl) pyrrolidine-1-carboxylate

[001834] To a solution of 2- (2-bromoacetyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate (4R) -tert-butyl (Example 200 step 2) (0, 1 g, 0.227 mmol) in dry tetrahydrofuran (1 mL) was added morpholine (0.020 mL, 0.227 mmol) at room temperature in one part. The reaction was stirred for 15 min and then diluted with diethyl ether (1 ml). The resulting solid was removed by filtration and the filtrate was evaporated to dryness to give 2- (2R-2-morpholinoacetyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate hydrobromide tert-butyl as viscous oil. Yield: 0.105 g, 88%.

[001835] Step 2: 2-morpholino-1 - ((4R) -4- (2,3,5,6- tetrafluorophenyl) pyrrolidin-2-yl) ethan-1-one dihydrochloride

[001836] 2- (2-Morpholinoacetyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate (4R) -tert-butyl hydrochloride (0.105 g, 0.199 mmol) was dissolved in HCl 4 M (0.996 mL, 3.98 mmol) in dioxane and the solution was stirred for 1 h. Thereafter, the mixture was diluted with diethyl ether (about 10 ml) and the resulting precipitate was aged for 30 min with stirring. The solid was collected, washed with diethyl ether and dried to give 2-morpholino-1 - ((4R) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidin-2-yl) ethanone dihydrochloride as a white powder . Yield: 0.083 g, 99%.

[001837] Step 3: (R) -1- (morpholinomethyl) -6- (2,3,5,6- tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole hydrochloride [1, 2-c] imidazole-3-thione

[001838] A mixture of 2-morpholino-1 - ((4R) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidin-2-yl) ethanone (0.078 g, 0.186 mmol), potassium isothiocyanate (0.027 g, 0.279 mmol) and cc HCl. (0.022 ml, 0.130 mmol) in a mixture of ethanol (1 ml) and water (1 ml) was stirred under reflux for 30 min. After that, the mixture was diluted with water (about 2 ml) and then the ethanol was removed in vacuo. The aqueous residue was neutralized by adding sodium bicarbonate solution and then extracted with dichloromethane. The organic phase was dried (MgSO4), filtered and evaporated to dryness. The oily residue was recovered with isopropanol (about 1 ml), acidified by adding 2 M HCl in diethyl ether and then diluted with diethyl ether to 10 ml. The resulting precipitate was collected, washed with diethyl ether and dried in vacuo at 50 ° C to give (R) -1- (morpholinomethyl) -6- (2,3,5,6-

tetrafluorophenyl) -6,7-dihydro-2H-pyrrolo [1,2-c] imidazole-3 (5H) -thione as an off-white powder, Yield: 0.050 g, 63%.

[001839] 1H NMR (DMSOd6): 12.07 (1 H, s), 11.58 (1 H, br s), 7.88 (1 H, m), 4.54 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, dd, J = 11.7, 9.2 Hz), 4.15 (2 H, m), 3.97 (2 H, br d, J = 12.5 Hz), 3.85 (1 H, dd, J = 11.7, 7.8 Hz), 3.78 (2 H, br t, J = 12.0 Hz), 3.52 ( 1 H, dd, J = 9.4, 16.3 Hz), 3.29 (2 H, br dd, J = 18.0, 13.4 Hz), 3.12 (1 H, dd, J = 16.4, 8.1 Hz), 3.04 (2 H, m). 13

[001840] C NMR (DMSOd6): 157.4, 146.4, 146.4, 146.3, 145.3, 145.2, 144.8, 144.7, 144.7, 143.7, 143.6, 135.6, 120, 108.2, 106, 105.9, 105.7, 63.1, 50.2, 48.9, 48.5, 35.6, 29.6.

[001841] Example 210: (R) -1- (pyrrolidin-1-ylmethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H- hydrochloride pyrrole [1,2-c] imidazole-3-thione

[001842] The compound was prepared in a manner analogous to Example 209 and isolated as an off-white powder.

[001843] 1H NMR (DMSOd6): 12.11 (1 H, s), 11.13 (1 H, br s), 7.87 (1 H, m), 4.53 (1 H, quin, J = 8.4 Hz), 4.23 (1 H, dd, J = 11.4, 9.4 Hz), 4.15 (2 H, br s), 3.84 (1 H, dd, J = 11.7, 7.6 Hz), 3.52 (1 H, br dd, J = 16.2, 9.3 Hz), 3.38 (2 H, m), 3.12 (1 H, br dd, J = 16.3, 7.8 Hz), 3.03 (2 H, br s), 1.99 (2 H, br s), 1.88 (2 H, br s). 13

[001844] C NMR (DMSOd6): 157, 146.4, 146.3, 146.3, 145.3,

145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 134.1, 120.3, 120.2, 111.1, 106, 105.8, 105.7, 52.2, 48.9, 46.1, 35.6, 29.5, 22.7.

[001845] Example 211: (R) -1 - ((((2-hydroxyethyl) (methyl) amino) methyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[001846] The compound was prepared in a manner analogous to Example 209 and isolated as a cream powder.

[001847] 1H NMR (DMSOd6): 12.10 (1 H, br s), 10.45 (1 H, br s), 7.88 (1 H, br s), 5.35 (1 H, br), 4.55 (1 H, m), 4.23 (1 H, dd, J = 11.5, 9.3 Hz), 4.17 (2 H, m), 3.85 (1 H , m), 3.77 (2 H, br t, J = 5.2 Hz), 3.49 (1 H, dt, J = 9.9, 16.3 Hz), 3.19 (1 H, m), 3.09 (1 H, m), 3.04 (1 H, m), 2.81 (0.5 H, br s), 2.72 (2.5 H, br t, J = 5.6 Hz). 13

[001848] C NMR (DMSOd6): 157.4, 146.4, 146.3, 146.2, 145.3, 145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 135.6, 120.2, 120.1, 120.1, 108.5, 108.5, 106, 105.8, 105.7, 56, 56, 55.2, 48.9, 48.6, 48.6, 42.4, 39, 35.6, 35.6, 29.6.

[001849] Example 212: (R) -1- (2- (pyridin-3-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -6,7-dihydro-2H-pyrrole [1,2-c] imidazole-3 (5H) -thione

[001850] Step 1: tert-Butyl (4R) -2- (2- (dimethoxyphosphoryl) acetyl) -4- (2,3,5,6- tetrafluorophenyl) pyrrolidine-1-carboxylate

[001851] To a solution of dimethyl methylphosphonate (0.655 mL, 6.04 mmol) in dry tetrahydrofuran (12 mL) was added N-butyllithium (4.15 mL, 6.65 mmol) (1.6 M in hexane) at -78 ° C, and the mixture was stirred for 30 min in the cold. After that, a solution of (4R) -1-tert-butyl 2-methyl-4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1,2-dicarboxylate (1.14 g, 3, 02 mmol) in tetrahydrofuran (12 mL), and the reaction mixture was stirred for 2 h in the cold. The reaction mixture was mitigated with saturated ammonium chloride solution and then extracted with ethyl acetate (20 ml). The organic phase was dried over MgSO4, filtered and evaporated to leave a colorless oil, which was purified by column chromatography in a mixture of petroleum ether - ethyl acetate to give 2- (2- (dimethoxyphosphoryl) acetyl) -4 - (4R) -tert-butyl (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate as a colorless oil. (Yield: 0.86 g, yield 60%).

[001852] Step 2: (4R) -2 - ((E) -3- (pyridin-3-yl) acryloyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate tert- butyl

[001853] To a solution of 2- (2- (dimethoxyphosphoryl) acetyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate (4R) -tert-butyl (0.2 g, 0.426 mmol) in ethanol (2.5 mL) was added potassium carbonate

(0.065 g, 0.469 mmol) and the mixture was stirred at room temperature for 15 min. Thereafter, 3-pyridinecarboxaldehyde (0.044 ml, 0.469 mmol) was added and stirring was continued for 2 h. The resulting solid was removed by filtration, the filtrate was evaporated to dryness and then purified by column chromatography in a mixture of petroleum ether - ethyl acetate to give 2 - ((E) -3- (pyridin-3 -yl) acryloyl) -4- (2,3,5,6-tetrafluorophenyl) (4R) - tert-butyl pyrrolidine-1-carboxylate as an oil. Yield: 0.19 g, 99%.

[001854] Step 3: tert-Butyl (4R) -2- (3- (pyridin-3-yl) propanoyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate

[001855] A 2 - ((E) -3- (pyridin-3-yl) acryloyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate solution of (4R) -tert- butyl (0.18 g, 0.400 mmol) in ethyl acetate (5 mL) was hydrogenated over 10% palladium on carbon (0.043 g, 0.040 mmol) for 7 h with an H2 flask. After that, the catalyst was filtered through a pad of celite and the filtrate was evaporated to give 2- (3- (pyridin-3-yl) propanoyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine- (4R) -tert-butyl 1-carboxylate as an oil. Yield: 0.16 g, 88%.

[001856] Step 4: (R) -1- (2- (pyridin-3-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) - 2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[001857] 2- (3- (Pyridin-3-yl) propanoyl) -4- (2,3,5,6-

(4R) -tert-butyl tetrafluorophenyl) pyrrolidine-1-carboxylate (0.16 g, 0.354 mmol) was dissolved in 4 M HCl (1.33 mL, 5.30 mmol) in dioxane and the solution was stirred for 1 H. The mixture was then diluted with diethyl ether (about 10 ml) to give a semi-solid precipitate. After that, the diethyl ether was decanted and the residue was dissolved in a mixture of ethanol (2 ml) and water (2 ml) followed by the addition of 6 M HCl (0.03 ml, 0.177 mmol) and potassium isothiocyanate (0.052 g, 0.530 mmol). The mixture was stirred at reflux for 30 min. After being cooled to room temperature, the pH was set to 7-8 by adding 1 M sodium hydroxide solution. The aqueous mixture was extracted with dichloromethane, the organic phase was dried (MgSO4), filtered and evaporated to dryness. . The residue was purified by chromatography on a mixture of dichloromethane - methanol to give (R) -1- (2- (pyridin-3-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -6, 7-dihydro-2H-pyrrolo [1,2-c] imidazole-3 (5H) -thione as an off-white powder. Yield: 0.049 g, 35%.

[001858] 1H NMR (DMSOd6): 11.87 (1 H, s), 8.38 (2 H, m), 7.84 (1 H, m), 7.57 (1 H, dt, J = 7.8, 2.0 Hz), 7.28 (1 H, dd, J = 7.8, 4.8 Hz), 4.40 (1 H, quin, J = 8.4 Hz), 4 , 12 (1 H, dd, J = 11.6, 9.1 Hz), 3.73 (1 H, dd, J = 11.7, 7.6 Hz), 3.08 (1 H, dd, J = 15.6, 9.2 Hz), 2.85 (2 H, m), 2.67 (2 H, t, J = 7.7 Hz), 2.65 (1 H, m). 13

[001859] C NMR (DMSOd6): 155.3, 149.6, 147.3, 146.4, 146.4, 146.3, 146.2, 146.2, 145.3, 145.2, 145.2, 145.2, 145.1, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.6, 143.6, 143.6, 143, 6, 143.5, 143.5, 143.5, 143.5, 136.1, 135.8, 127.9, 123.3, 120.4, 120.3, 120.2, 118.6, 105.8, 105.7, 105.5, 48.2, 35.8, 30.8, 28.8, 25.4.

[001860] Example 213: (R) -1- (2- (pyridin-2-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[001861] The compound was prepared in a manner analogous to Example 212 and isolated as an off-white powder.

[001862] 1H NMR (DMSOd6): 11.85 (1 H, s), 8.45 (1 H, m), 7.84 (1 H, m), 7.66 (1 H, td, J = 7.6, 1.9 Hz), 7.20 (1 H, d, J = 7.8 Hz), 7.17 (1 H, ddd, J = 7.4, 4.9, 1.0 Hz), 4.39 (1 H, quin, J = 8.4 Hz), 4.11 (1 H, dd, J = 11.6, 9.1 Hz), 3.71 (1 H, dd, J = 11.7, 7.6 Hz), 3.11 (1 H, dd, J = 15.6, 9.3 Hz), 2.98 (2 H, m), 2.78 (2 H, m), 2.66 (1 H, dd, J = 15.6, 7.8 Hz). 13

[001863] C NMR (DMSOd6): 159.9, 155.1, 148.9, 146.4, 146.3, 146.2, 145.2, 145.1, 145.1, 145.1, 145.1, 144.8, 144.7, 144.7, 144.6, 144.6, 144.6, 143.6, 143.6, 143.5, 143.5, 143.5, 143, 5, 136.4, 127.7, 122.8, 121.4, 120.5, 120.4, 120.3, 119, 105.8, 105.7, 105.5, 48.2, 35, 8, 35.7, 28.9, 23.6.

[001864] Example 214: (R) -6- (3-bromo-2,6-difluorophenyl) -1- (2- (pyridin-3-yl) ethyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[001865] The compound was prepared in a manner analogous to Example 212 and isolated as a cream powder.

[001866] 1H NMR (DMSOd6): 11.86 (1 H, s), 8.39 (2 H, m), 7.71 (1 H, ddd, J = 5.9, 8.1, 8 , 7 Hz), 7.57 (1 H, dt, J = 7.9, 2.0 Hz), 7.28 (1 H, ddd, J = 7.8, 4.8, 0.8 Hz) , 7.15 (1 H, m), 4.36 (1 H, m), 4.10 (1 H, m), 3.67 (1 H, dd, J = 11.6, 7.8 Hz ), 3.04 (1 H, dd, J = 15.6, 9.2 Hz), 2.85 (2 H, m), 2.67 (2 H, t, J = 7.7 Hz), 2.61 (1 H, dd, J = 15.6, 8.2 Hz). 13

[001867] C NMR (DMSOd6): 160.7, 160.7, 159.1, 159, 157.5, 157.4, 155.9, 155.8, 155.2, 149.6, 147, 3, 136.1, 135.8, 132.4, 132.4, 128.1, 123.3, 118.7, 118.6, 118.5, 113.8, 113.7, 113.6, 113.6, 104, 104, 103.9, 103.9, 48.4, 35.7, 30.8, 28.9, 25.4.

[001868] Example 215: (S) -6- (3-chloro-2,6-difluorophenyl) -1- (2- (pyridin-3-yl) ethyl) -2,5,6,7-tetrahydrochloride -hydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[001869] The compound was prepared in a manner analogous to Example 212 and isolated as an off-white solid.

[001870] 1H NMR (DMSOd6): 11.86 (1 H, s), 8.64 (2 H, m), 8.09 (1 H, br d, J = 7.8 Hz), 7, 73 (1 H, dd, J = 7.7, 5.5 Hz), 7.61 (1 H, m), 7.21 (1 H, m), 4.38 (1 H, quin, J = 8.5 Hz), 4.11 (1 H, dd, J = 11.2, 9.4 Hz), 3.68 (1 H, dd, J = 11.6, 7.6 Hz), 3, 11 (1 H, br dd, J = 15.6, 9.3 Hz), 2.99 (2 H, m), 2.73 (2 H, t, J = 7.5 Hz), 2.67 (1 H, dd, J = 15.7, 7.9 Hz). 13

[001871] C NMR (DMSOd6): 160.1, 160, 158.4, 158.4, 156.5, 156.4, 155.3, 154.9, 154.8, 144.5, 142, 7, 142, 138.8, 129.7, 129.6, 128.3, 125.5, 118.9, 118.8, 118.6, 118, 116.1, 116, 115.9, 115, 9, 113.2, 113.2, 113.1, 113.1, 48.4, 35.6, 30.5, 28.9, 24.9.

[001872] Example 216: (R) -1- (3-ethoxypropyl) -6- (2,3,5,6-

tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[001873] The compound was prepared analogously to Example 212 and isolated as a white powder.

[001874] 1H NMR (DMSOd6): 11.77 (1 H, s), 7.85 (1 H, m), 4.50 (1 H, quin, J = 8.4 Hz), 4.16 (1 H, dd, J = 11.5, 9.2 Hz), 3.76 (1 H, dd, J = 11.7, 7.6 Hz), 3.36 (2 H, m), 3 , 31 (3 H, m), 2.90 (1 H, dd, J = 15.7, 7.8 Hz), 2.38 (2 H, t, J = 7.5 Hz), 1.73 (2 H, quin, J = 6.9 Hz), 1.07 (3 H, t, J = 7.0 Hz). 13

[001875] C NMR (DMSOd6): 155.1, 146.4, 146.4, 146.3, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144.6, 143.7, 143.6, 143.6, 127, 5, 120.6, 120.5, 120.4, 119.2, 105.8, 105.7, 105.5, 68.5, 65.2, 48.3, 35.8, 28.9, 27.7, 20.8, 15.1.

[001876] Example 217: (R) -1- (2- (1-methyl-1H-imidazol-2-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[001877] The compound was prepared analogously to Example 212 and isolated as a light beige powder.

[001878] 1H NMR (DMSOd6): 11.89 (1 H, br s), 7.85 (1 H, m), 6.99 (1 H, s), 6.72 (1 H, s) , 4.43 (1 H, quin, J = 8.5 Hz), 4.14 (1 H, dd, J = 9.4, 11.3 Hz), 3.75 (1 H, br dd, J = 11.5, 8.0 Hz), 3.51 (3 H, s), 3.18 (1 H, br dd, J = 15.6, 9.4 Hz), 2.85 (2 H, dd, J = 7.1, 8.8 Hz), 2.79 (1 H, br dd, J = 15.6, 8.1 Hz), 2.73 (2 H, dd, J = 7.1 , 8.8 Hz). 13

[001879] C NMR (DMSOd6): 155.1, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.7, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 143.5, 127.9, 126.1, 121, 120.3, 119, 105.9, 105.7, 105.6, 48.2, 35.8, 32, 28.7, 24.9, 22.2.

[001880] Example 218: (R) -1- (2- (pyridin-4-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[001881] The compound was prepared in a manner analogous to Example 212 and isolated as a light yellow powder.

[001882] 1H NMR (DMSOd6): 11.87 (1 H, s), 8.43 (2 H, m), 7.84 (1

H, m), 7.19 (2 H, m), 4.41 (1 H, quin, J = 8.4 Hz), 4.13 (1 H, dd, J = 11.6, 9.1 Hz), 3.73 (1 H, dd, J = 11.7, 7.5 Hz), 3.13 (1 H, dd, J = 15.7, 9.4 Hz), 2.85 (2 H, m), 2.68 (3 H, m). 13

[001883] C NMR (DMSOd6): 155.3, 149.6, 149.5, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 146.2, 145.3, 145.2, 145.2, 145.2, 145.2, 145.1, 145.1, 145.1, 144.8, 144.8, 144.7, 144.7, 144, 7, 144.6, 144.6, 143.6, 143.6, 143.6, 143.5, 143.5, 143.5, 143.5, 127.9, 123.8, 120.5, 120.4, 120.3, 118.5, 105.9, 105.7, 105.6, 48.3, 35.8, 32.8, 28.9, 24.6.

[001884] Example 219: (R) -1- (3- (pyrrolidin-1-yl) propyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydrochloride -hydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[001885] The compound was prepared in an analogous manner to Example 35 from (R) -1- (pyrrolidin-1-yl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo - 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one (Example 204) and isolated as a yellowish powder.

[001886] 1H NMR (DMSOd6): 11.86 (1 H, br s), 10.76 (1 H, br s), 7.87 (1 H, m), 4.51 (1 H, quin , J = 8.5 Hz), 4.16 (1 H, dd, J = 11.4, 9.3 Hz), 3.77 (1 H, br dd, J = 11.6, 7.8 Hz ), 3.49 (2 H, m), 3.34 (1 H, dd, J = 6.4, 11.7 Hz), 3.05 (2 H, m), 2.96 (1 H, dd, J = 8.0, 15.8 Hz), 2.93 (2 H, m), 2.46 (2 H, br t, J = 7.4 Hz), 1.95 (4 H, m ), 1.87 (2 H, m). 13

[001887] C NMR (DMSOd6): 155.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143, 7, 143.7, 143.6,

143.6, 143.6, 143.6, 143.5, 128, 120.4, 120.3, 120.2, 118.2, 105.9, 105.7, 105.6, 53, 52, 8, 48.3, 35.8, 28.9, 23.9, 22.6, 21.3.

[001888] Example 220: (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [1, 2-c] imidazol-1-yl) methyl) cyclopropanecarboxamide

[001889] Step 1: (S) -1- (aminomethyl) -6- (3-chloro-2,6-difluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1,2- c] imidazole-3-thione

[001890] To a stirred solution of (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [ 1,2-c] imidazol-1-yl) acetic acid (1 g, 2.90 mmol) in a mixture of Toluene (20 mL) and ethanol (0.85 mL, 14.50 mmol) was added triethylamine (0, 48 mL, 3.48 mmol) followed by dropwise addition of diphenyl phosphorazidate (0.75 mL 3.48 mmol) at room temperature.

[001891] The reaction mixture was heated to reflux for 3 h. The solvent was then removed under reduced pressure and the obtained crude oil was purified by column chromatography in a mixture of dichloromethane - methanol. The oil obtained was dissolved in 2 ml of methanol and treated with 2 ml of 1 M potassium hydroxide solution and the reaction was stirred at room temperature overnight. After that, the mixture was diluted with water and extracted with a mixture of dichloromethane: isopropanol (7: 3). The organic phase was evaporated to dryness and the product was purified by chromatography. Yield: 74 mg, 8%.

[001892] Step 2: (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazol-1-yl) methyl) cyclopropanecarboxamide

[001893] To a stirred solution of (S) -1- (aminomethyl) -6- (3-chloro-2,6-difluorophenyl) -6,7-dihydro-2H-pyrrole [1,2-c] imidazole-3 (5H) -thione (70 mg, 0.222 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.042 mL, 0.244 mmol) was added cyclopropanecarbonyl chloride (0.024 mL, 0.266 mmol) and the reaction was stirred for 1 h at room temperature. The reaction was then diluted with 10 ml of dichloromethane, washed with 1 M HCl and concentrated NaHCO3, respectively. The organic phase was dried over MgSO4, filtered and evaporated to dryness. The residue was dissolved in 2 ml of 4 N HCl in dioxane and stirred overnight at room temperature. After that, the solvent was removed in vacuo and the crude product was purified by column chromatography in a mixture of dichloromethane - methanol. Trituration in diethyl ether gave (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [1, 2-c] imidazol-1-yl) methyl) cyclopropanecarboxamide as an off-white solid. Yield: 16 mg, 18%.

[001894] 1H NMR (DMSOd6): 11.81 (1 H, br s), 8.40 (1 H, t, J = 5.4 Hz), 7.62 (1 H, m), 7, 22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.5, 9.2 Hz), 4.02 ( 2 H, m), 3.72 (1 H, dd, J = 11.7, 7.8 Hz), 3.24 (1 H, dd, J = 15.8, 9.4 Hz), 2, 87 (1 H, dd, J = 15.8, 8.1 Hz), 1.55 (1 H, m), 0.64 (4 H, m). 13

[001895] C NMR (DMSOd6): 172.7, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.5, 154.9, 154.9, 129.7, 129.7, 128.9, 118.8, 118.7, 118.6, 117.5, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 48.5, 35.6, 33.2, 29.2, 13.4, 6.3, 6.3.

[001896] Example 221: (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo-

3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) methyl) cyclopropanecarboxamide

[001897] Step 1: (S) -1- (aminomethyl) -6- (3-chloro-2,6-difluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole hydrochloride [1, 2-c] imidazole-3-thione

[001898] To a stirred solution of (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [ 1,2-c] imidazol-1-yl) acetic acid (1 g, 2.90 mmol) in 1,4-Dioxane (100 mL) was added in triethylamine (0.404 mL, 2.90 mmol) followed by the addition of phosphorazidate diphenyl (0.686 ml, 3.19 mmol) and the reaction was stirred at room temperature for 30 min. The above mixture was added dropwise to a preheated solution (80 ° C) of formic acid (0.657 ml, 17.30 mmol) and hydrogen chloride (5.80 ml, 5.80 mmol) in 1.4 - Dioxane (100 mL). The reaction was stirred in the hot 90 min and then cooled to room temperature. The solvent was removed in vacuo and the residue was azeotroped with isopropanol. Recrystallization from an isopropanol-diethyl ether mixture gave (S) -1- (aminomethyl) -6- (3-chloro-2,6-difluorophenyl) -6,7-dihydro-2H-pyrrole hydrochloride [1,2-c] imidazole-3 (5H) -thione. Yield: 395 mg, 38%.

[001899] Step 2: (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazol-1-yl) methyl) cyclopentanecarboxamide

[001900] To a stirred solution of (S) -1- (aminomethyl) -6- (3-chloro-2,6-difluorophenyl) -6,7-dihydro-2H-pyrrole hydrochloride [1,2- c] imidazole-3 (5H) -thione (75 mg, 0.213 mmol) in dichloromethane (2 mL) was added N-ethyl-N-isopropylpropan-2-amine (DIPEA) (0.076 mL, 0.426 mmol). After being stirred for 15 min at room temperature, cyclopentanecarboxylic acid (36.5 mg, 0.319 mmol) was added, followed by the addition of 2,4,6-2,4,6-tripropyl-1,3,5, 2,4,6-trioxatrifosfinan (0.198 ml, 0.319 mmol). The reaction was stirred overnight at room temperature. After that, the mixture was diluted with 10 ml of dichloromethane, washed with 1 M HCl, saturated NaHCO3 and saline, respectively. The organics were dried over MgSO4, filtered and evaporated to dryness. Chromatography on a mixture of dichloromethane - isopropanol gave (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H- pyrrolo [1,2-c] imidazol-1-yl) methyl) cyclopentanecarboxamide as an off-white solid. Yield: 31 mg, 35%.

[001901] 1H NMR (DMSOd6): 11.79 (1 H, s), 8.11 (1 H, t, J = 5.5 Hz), 7.61 (1 H, m), 7.21 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.14 (1 H, dd, J = 11.3, 9.4 Hz), 4.01 (2 H, m), 3.71 (1 H, dd, J = 11.7, 7.8 Hz), 3.24 (1 H, dd, J = 15.8, 9.4 Hz), 2.85 (1 H, dd, J = 15.8, 7.9 Hz), 2.50 (1 H, m), 1.70 (2 H, m), 1.58 (4 H, m), 1, 47 (2 H, m). 13

[001902] C NMR (DMSOd6): 175.4, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.3, 154.9, 154.9, 129.7, 129.6, 128.7, 118.9, 118.7, 118.6, 117.7, 116.1, 116.1, 116, 115.9, 113.3, 113.2, 113.1, 113.1, 48.5, 44.1, 35.6, 33, 29.9, 29.9, 29.3, 25.6.

[001903] Example 222: (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazol-1-yl) methyl) tetrahydro-2H-pyran-4-carboxamide

[001904] The compound was prepared analogously to Example 221 from (S) -1- (aminomethyl) -6- (3-chloro-2,6-difluorophenyl) hydrochloride - 2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione and isolated as an off-white solid.

[001905] 1H NMR (DMSOd6): 11.80 (1 H, br s), 8.14 (1 H, br t, J = 5.4 Hz), 7.61 (1 H, m), 7 , 22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.5, 9.3 Hz), 4.02 (2 H, m), 3.83 (2 H, m), 3.71 (1 H, dd, J = 11.6, 7.8 Hz), 3.25 (3 H, m), 2, 85 (1 H, dd, J = 15.8, 8.1 Hz), 2.35 (1 H, m), 1.54 (4 H, m). 13

[001906] C NMR (DMSOd6): 174, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.3, 154.9, 154.9, 129, 7, 129.6, 128.7, 118.9, 118.8, 118.6, 117.5, 116, 115.9, 113.3, 113.2, 113.1, 113.1, 66, 4, 48.5, 40.6, 35.6, 33, 29.2, 28.8.

[001907] Example 223: (S) -N - ((6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazol-1-yl) methyl) nicotinamide

[001908] The compound was prepared analogously to Example 221 from (S) -1- (aminomethyl) -6- (3-chloro-2,6-difluorophenyl) hydrochloride - 2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione and isolated as an off-white solid.

[001909] 1H NMR (DMSOd6): 11.90 (1 H, br s), 9.03 (1 H, t, J = 5.4 Hz), 9.00 (1 H, dd, J = 2 , 3, 0.8 Hz), 8.70 (1 H, dd, J = 4.8, 1.7 Hz), 8.18 (1 H, dt, J = 8.1, 1.9 Hz) , 7.60 (1 H, m), 7.50 (1 H, ddd, J = 7.9, 4.8, 0.7 Hz), 7.20 (1 H, m), 4.44 ( 1 H, quin, J = 8.6 Hz), 4.27 (2 H, m), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 3.72 (1 H , dd, J = 11.7, 7.9 Hz), 3.26 (1 H, dd, J = 15.8, 9.4 Hz), 2.88 (1 H, dd, J = 15.8 , 8.1 Hz). 13

[001910] C NMR (DMSOd6): 165, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.6, 154.9, 154.9, 152, 148.4, 135, 129.7, 129.6, 129.5, 129, 123.5, 118.7, 118.6, 118.5, 117, 116.1, 116, 115.9, 115, 9, 113.2, 113.2, 113.1, 113.1, 48.5, 35.6, 33.7, 29.2.

[001911] Example 224: 2 - {[(6S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazol-1-yl] methyl} -1-cyanoguanidine

[001912] To a stirred suspension of (S) -1- (aminomethyl) -6- (3-bromo-2,6-difluorophenyl) -6,7-dihydro-2H-pyrrole hydrochloride [1,2- c] imidazole-3 (5H) -thione (prepared analogously to Example 221 step 1) (0.23 g, 0.580 mmol) in tetrahydrofuran (29.0 mL) N-ethyl-N-isopropylpropane- was added 2-amine (DIPEA) (0.203 mL, 1,160 mmol), followed by rapid addition of diphenyl N-cyanocarbonimidate (0.276 g, 1.116 mmol) and then the reaction was stirred for 30 min at room temperature. After that, 7 M ammonia in methanol (4.14 mL, 29.0 mmol) was added and the mixture was heated to 80 ° C overnight in a sealed tube. After that, the reaction was cooled to room temperature and evaporated to dryness under reduced pressure. Chromatography on a mixture of dichloromethane - methanol gave the product as a light yellow solid.

[001913] 1H NMR (DMSOd6): 11.83 (1 H, s), 7.73 (1 H, m), 7.17 (1 H, m), 6.97 (1 H, s br) , 6.81 (2 H, s br), 4.47 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, m), 4.03 (2 H, m), 3 , 72 (1 H, dd, J = 11.6, 7.9 Hz), 3.25 (1 H, dd, J = 9.4, 15.7 Hz), 2.86 (1 H, dd, J = 15.8, 8.1 Hz). 13

[001914] C NMR (DMSOd6): 161.1, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155.7, 132.5, 132.4, 129.2, 118.8, 118.6, 118.5, 117.8, 116.9, 113.8, 113.8, 113.6, 113.6, 104, 1, 103.9, 48.5, 35.6, 35, 29.3.

[001915] Example 225: (S, Z) -N - ((6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [ 1,2-c] imidazol-1-yl) methyl) -N'- cyanopyrrolidine-1-carboxyidamide

[001916] The compound was prepared in a manner analogous to Example 224 and isolated as a dark yellow solid.

[001917] 1H NMR (DMSOd6): 11.74 (1 H, s), 7.73 (1 H, m), 7.17 (1 H, m), 7.04 (0.8 H, t , J = 5.6 Hz), 6.87 (0.2 H, s), 4.45 (1 H, quin, J = 8.7 Hz), 4.24-4.09 (2.6 H , m), 3.98 (0.4 H, t, J = 6.1 Hz), 3.71 (1 H, dd, J =

11.7, 8.0 Hz), 3.47 (3.2 H, br s), 3.30-3.16 (1.8 H, m), 2.90 (1 H, m), 1 , 84, 1.77 (4 H, m). 13

[001918] C NMR (DMSOd6): 160.8, 160.8, 159.2, 159.1, 158.6, 157.5, 157.5, 156.3, 155.9, 155.9, 155.6, 155.5, 132.5, 132.4, 129, 119.1, 118.7, 118.6, 118.6, 118.5, 118.3, 117.4, 117.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.5, 47.8, 36.2, 35.6, 29.2, 24.8.

[001919] Example 226: (S) -N- (2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [ 1,2-c] imidazol-1-yl) ethyl) -N- methylnicotinamide

[001920] The compound was prepared analogously to Example 168 from (S) -6- (3-chloro-2,6-difluorophenyl) -1- (2- (methylamino) ethyl) -6.7 hydrochloride -dihydro-2H-pyrrolo [1,2-c] imidazole-3 (5H) -thione (Example 193) and isolated as an off-white solid.

[001921] 1H NMR (DMSOd6): 11.93 (0.5 H, br s), 11.64 (0.5 H, br s), 8.63 (0.5 H, br d, J = 4.0 Hz), 8.59 (0.5 H, br d, J = 4.0 Hz), 8.57 (0.5 H, br s), 8.43 (0.5 H, s) , 7.78 (05 H, br d, J = 7.6 Hz), 7.62 (1 H, m), 7.51 (0.5 H, br d, J = 7.6 Hz), 7 , 45 (0.5 H, br dd, J = 7.0, 5.3 Hz), 7.42 (0.5 H, m), 7.21 (1 H, m), 4.46 (0 , 5 H, m), 4.37 (0.5 H, quin, J = 8.5 Hz), 4.15 (1 H, m), 3.73 (1 H, m), 3.65 ( 1 H, m), 3.41 (1 H, m), 3.31 (0.5 H, m), 3.01 (0.5 H, dd, J = 9.2, 15.8 Hz) , 2.97 (1.5 H, s), 2.91 (1 H, dd, J = 7.9, 15.6 Hz), 2.87 (1.5 H, s), 2.70 ( 1 H, m), 2.53 (1 H, m). 13

[001922] C NMR (DMSOd6): 168.3, 167.8, 160.1, 160.1, 158.5, 158.4, 156.5, 156.5, 155.5, 155.5, 155.4, 154.9, 154.8, 150.3, 150, 147.5, 146.9, 134.5, 134.2, 132.2, 132.1, 129.7, 129.7, 129.6, 128.9, 128.8, 128.7, 123.5, 123.4, 118.8, 118.7, 118.6, 118.5, 118.4, 118.3,

116.9, 116.1, 116.1, 116, 115.9, 115.9, 113.2, 113.1, 49.9, 48.5, 48.3, 45.9, 37.3, 35.7, 32.5, 28.9, 28.6, 22.7, 21.9.

[001923] Example 227: (S) -N- (2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [ 1,2-c] imidazol-1-yl) ethyl) -N-methylpyrrolidine-1-carboxamide

[001924] To a stirred suspension of (S) -6- (3-chloro-2,6-difluorophenyl) -1- (2- (methylamino) ethyl) -6,7-dihydro-2H-pyrrole hydrochloride [1,2- c] imidazole-3 (5H) -thione (Example 193) (87 mg, 0.229 mmol in pyridine (2 mL), pyrrolidine-1-carbonyl chloride (0.030 mL, 0.275 mmol) was added and the reaction The mixture was stirred at room temperature overnight The reaction was diluted with dichloromethane (10 ml) and washed three times with 5 ml 1 M HCl. The organic phase was dried over MgSO4, filtered and evaporated to dryness. crude product was purified by chromatography on a mixture of dichloromethane - methanol Crystallization from ethyl acetate gave (S) -N- (2- (6- (3-chloro-2,6-difluorophenyl) -3 -thioxy-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethyl) -N-methylpyrrolidine-1-carboxamide as a white solid Yield: 23 mg , 22%.

[001925] 1H NMR (DMSOd6): 11.82 (1 H, s), 7.62 (1 H, m), 7.22 (1 H, m), 4.42 (1 H, quin, J = 8.7 Hz), 4.12 (1 H, dd, J = 9.5, 11.2 Hz), 3.72 (1 H, dd, J = 11.5, 8.1 Hz), 3 , 30 (2 H, t, J = 7.0 Hz), 3.24 (1 H, dd, J = 15.6, 9.2 Hz), 3.16 (4 H, m), 2.86 (1 H, dd, J = 15.6, 8.4 Hz), 2.71 (3 H, s), 2.56 (2 H, br t, J = 7.0 Hz), 1.71 ( 4 H, m). 13

[001926] C NMR (DMSOd6): 161.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 155, 154.9, 129, 7, 129.7, 128.5, 118.7, 118.5,

118.4, 117.3, 116.1, 116.1, 116, 115.9, 113.3, 113.2, 113.1, 113.1, 48.3, 48.1, 47.9, 36, 35.7, 28.9, 25.1, 22.4.

[001927] Example 228: (S) -6- (3-chloro-2,6-difluorophenyl) -1 - ((3-methyl-1,2,4-oxadiazol-5-yl) methyl) -6.7 -dihydro-2H-pyrrolo [1,2-c] imidazole-3 (5H) - thiona

[001928] To a stirred suspension of (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole acid [ 1,2-c] imidazol-1-yl) acetic acid (150 mg, 0.435 mmol) in dioxane (3 ml) 3 - (((ethylimino) methylene) amino) -N, N-dimethylpropan-1- hydrochloride amine (113 mg, 0.592 mmol) in one part and the reaction mixture was stirred for 30 min at room temperature. After that, the obtained solution was treated with N-hydroxyacetimidamide (32.2 mg, 0.435 mmol) and the reaction mixture was stirred for 1 h at room temperature followed by stirring at 110 ° C for an additional 3.5 h. The solvent was then removed in vacuo and the residue was diluted with ethyl acetate (25 ml), twice with sodium bicarbonate solution (25 ml) and water (25 ml), respectively. The organic phase was dried over MgSO4, filtered and evaporated to dryness. Purification by chromatography (reverse phase, acetonitrile-water mixture) followed by recrystallization from isopropanol gave (S) -6- (3-chloro-2,6-difluorophenyl) -1 - ((3-methyl-1,2 , 4-oxadiazol-5-yl) methyl) -6,7-dihydro-2H-pyrrolo [1,2-c] imidazole-3 (5H) -thione as an off-white solid. Yield: 0.058 g, 34%.

[001929] 1H NMR (DMSOd6): 11.97 (1 H, s), 7.61 (1 H, m), 7.21 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.18 (1 H, dd, J = 9.3, 11.7 Hz), 4.15 (2 H, m), 3.75 (1 H, dd, J = 11 , 6, 7.8 Hz), 3.25 (1 H, dd, J = 15.9, 9.3 Hz), 2.86 (1 H, dd, J = 15.9, 8.0 Hz) , 2.31 (3 H, s).

[001930] C NMR (DMSOd6): 175.9, 167.1, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.1, 154.9, 154.9, 130.2, 129.7, 129.7, 118.8, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 112, 48.7, 35.6, 29, 22, 11.1.

[001931] Example 229: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H- acid pyrrole [1,2-c] imidazol-1-yl) acetic

[001932] Step 1: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo- 2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) ethyl acetate

[001933] To a solution of 2- (3-ethoxy-3-oxopropanoyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine-1-carboxylate of (4R) -tert-butyl (3.22 g , 5.57 mmol) in dichloromethane (50 mL), trifluoroacetic acid (8.59 mL, 111 mmol) was added in one part and the solution was stirred for 5 h at room temperature. After that, the mixture was mitigated with ice-cooled sodium bicarbonate solution. The organic phase was dried over MgSO4, filtered and treated with methyl isothiocyanate (0.489 g, 6.69 mmol) followed by addition of triethylamine (0.78 mL, 5.57 mmol). The solution was stirred for 64 h at room temperature and then evaporated to dryness. The residue was dissolved in abs ethanol. (50 mL) followed by addition of cc HCl. (1.39 mL, 16.72 mmol) and the mixture was stirred at reflux for 1 h. Thereafter the solvent was removed and the residue was partitioned between dichloromethane and water. The organic phase was dried (MgSO4), filtered and evaporated. Chromatography in a mixture of petroleum ether - ethyl acetate followed by slurries in petroleum ether gave 2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3, 5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) (R) -ethyl acetate as colorless solid. Yield: 0.25 g, 11%.

[001934] Step 2: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H- acid pyrrole [1,2-c] imidazol-1-yl) acetic

[001935] To a solution of 2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [1, 2-c] imidazol-1-yl) (R) - ethyl acetate (0.25 g, 0.644 mmol) in methanol (7 mL) 1 N NaOH (0.97 mL, 0.966 mmol) was added (gentle heating and sonication to obtain a clear solution) and the mixture was stirred for 3 h at room temperature. The methanol was then removed in vacuo, the residue was diluted with water to approx. 10 mL, acidified by adding 6 M HCl to pH = 1-2. The resulting precipitate was collected, washed with water, dried in vacuo at 50 ° C to give (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-3 acid , 5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) acetic as an off-white powder. Yield: 0.21 g, 91%.

[001936] 1H NMR (DMSOd6): 12.74 (1 H, s br), 7.86 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4, 25 (1 H, dd, J = 11.6, 9.2 Hz), 3.85 (1 H, dd, J = 11.7, 7.6 Hz), 3.65 (2 H, s), 3.40 (3 H, s), 3.35 (1 H, m), 2.95 (1 H, dd, J = 16.0, 7.8 Hz). 13

[001937] C NMR (DMSOd6): 170.8, 156.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.6, 143.6, 143.6, 128.5, 120.5, 120.4, 120.3, 115, 6, 105.9, 105.7, 105.6, 49.5, 34.8, 31.4, 29.8, 29.

[001938] Example 230: (S) -2- (6- (5-chloro-2-fluorophenyl) -2-methyl-3- acid

thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic

[001939] The compound was prepared analogously to Example 229 from 2- (3-ethoxy-3-oxopropanoyl) -4- (5-chloro-2-fluorophenyl) pyrrolidine-1-carboxylate (4S) -tert -butyl and isolated as a beige solid.

[001940] 1H NMR (DMSOd6): 12.70 (1 H, br s), 7.47 (1 H, dd, J = 6.5, 2.6 Hz), 7.40 (1 H, ddd , J = 8.7, 4.4, 2.6 Hz), 7.29 (1 H, dd, J = 9.9, 8.9 Hz), 4.21 (2 H, m), 3, 81 (1 H, m), 3.67 (2 H, s), 3.39 (3 H, m), 3.27 (1 H, br dd, J = 15.6, 7.5 Hz), 2.93 (1 H, dd, J = 15.5, 7.3 Hz). 13

[001941] C NMR (DMSOd6): 170.8, 159.8, 158.2, 156.6, 130.2, 130.1, 128.9, 128.9, 128.7, 128.5, 128.5, 128.5, 117.6, 117.4, 115.8, 50.2, 31.4, 29.8, 29.3.

[001942] Example 231: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6- hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic

[001943] The compound was prepared in a manner analogous to

Example 229 from (1S, 5R) -1- (3-chloro-2,6-difluorophenyl) -4- (3-ethoxy-3-oxopropanoyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate tert-butyl and isolated as a beige solid.

[001944] 1H NMR (DMSOd6): 12.78 (1 H, br s), 7.64 (1 H, m), 7.21 (1 H, t, J = 8.9 Hz), 4, 12 (1 H, d, J = 12.2 Hz), 3.81 (1 H, d, J = 12.0 Hz), 3.74 (2 H, m), 3.36 (3 H, s ), 2.85 (1 H, dd, J = 8.2, 4.4 Hz), 1.70 (1 H, dd, J = 8.1, 5.6 Hz), 1.27 (1 H , t, J = 5.0 Hz). 13

[001945] C NMR (DMSOd6): 170.9, 161.2, 161.2, 159.6, 159.6, 157.8, 157.8, 157, 156.2, 156.1, 117, 116.9, 116.8, 115.8, 115.7, 115.6, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 52.3, 31, 4, 29.8, 25.7, 21.7, 21.1.

[001946] Example 232: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[001947] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[001948] 1H NMR (DMSOd6): 8.38 (1 H, br d, J = 6.6 Hz), 7.73 (1 H, m), 7.17 (1 H, m), 4, 44 (1 H, quin, J = 8.6 Hz), 4.22 (2 H, m), 3.78 (2 H, m), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, m), 3.46 (1 H, dd, J = 8.9, 3.5 Hz), 3.43 (2 H, m), 3.40 (3 H, s), 3.28 (1 H, dd, J = 15.8, 9.5 Hz), 2.88 (1 H, dd, J = 15.8, 8.1 Hz), 2 , 07 (1 H, m), 1.71 (1 H, m).

[001949] C NMR (DMSOd6): 167.6, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.4, 118.8, 118.7, 118.6, 116.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 1, 103.9, 103.9, 72.4, 66.3, 49.8, 49.6, 34.8, 32, 31.5, 31.1, 29.2.

[001950] Example 233: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1-morpholinoetan-1-one

[001951] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[001952] 1H NMR (DMSOd6): 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 9.3, 11.2 Hz), 3.79 (1 H, br dd, J = 11.6, 7.6 Hz), 3.75 (2 H, s), 3.59 (2 H, m), 3.55 (2 H, m), 3.49 (2 H, m), 3.45 (2 H, m), 3.36 (3 H, m), 3.27 (1 H, dd, J = 15.8, 9.4 Hz), 2.85 (1 H, dd, J = 15.8, 7.8 Hz). 13

[001953] C NMR (DMSOd6): 166.8, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.3, 118.9, 118.8, 118.6, 116.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 66, 66, 49.5, 45.6, 41.7, 34.8, 31.5, 29.2, 28.8.

[001954] Example 234: 1 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) cyclopropane-1-carboxamide

[001955] The compound was prepared in an analogous manner to Example 32 from (S) - (1- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) cyclopropyl) (1H-imidazol-1-yl) methanone and isolated as a white powder.

[001956] 1H NMR (DMSOd6): 7.74 (1 H, m), 7.63 (1 H, d, J = 6.9 Hz), 7.18 (1 H, m), 4.41 (1 H, quin, J = 8.9 Hz), 4.32 (1 H, m), 4.21 (1 H, dd, J = 9.3, 11.3 Hz), 3.84-3 , 74 (2 H, m), 3.72 (1 H, dd, J = 8.8, 6.7 Hz), 3.63 (1 H, m), 3.46 (1 H, dd, J = 8.8, 4.8 Hz), 3.35 (3 H, s), 3.24 (1 H, dd, J = 15.6, 9.0 Hz), 2.97 (1 H, dd , J = 15.6, 9.0 Hz), 2.04 (1 H, m), 1.76 (1 H, m), 1.43 (1 H, m), 1.35 (1 H, m), 1.02 (2 H, m). 13

[001957] C NMR (DMSOd6): 170.4, 161, 160.9, 159.3, 159.3, 157.7, 157.6, 156.5, 156.1, 156, 132.6, 132.5, 130.9, 119.3, 118, 117.9, 117.7, 113.8, 113.8, 113.6, 113.6, 104.1, 103.9, 71.5, 66.6, 50.3, 49.2, 35.1, 32, 31.4, 29, 22.1, 15.5, 15.1.

[001958] Example 235: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1- (1,1-dioxidothiomorpholine) ethan-1-one

[001959] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a white solid.

[001960] 1H NMR (DMSOd6): 7.73 (1 H, ddd, J = 8.8, 8.1, 5.8 Hz), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, dd, J = 11.2, 9.5 Hz), 3.90 (2 H, m), 3.87 (2 H, m), 3.85 (2 H, s), 3.80 (1 H, dd, J = 11.6, 7.8 Hz), 3.36 (3 H, s), 3.31 (2 H , m), 3.28 (1 H, dd, J = 9.3, 15.8 Hz), 3.13 (2 H, m), 2.86 (1 H, dd, J = 15.9, 8.0 Hz). 13

[001961] C NMR (DMSOd6): 167.2, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.3, 155.9, 155.9, 132.5, 132.4, 128.5, 118.8, 118.7, 118.6, 116, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103, 9, 103.9, 51.1, 51, 49.6, 43.7, 40.2, 34.8, 31.6, 29.2, 28.8.

[001962] Example 236: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- isopropylacetamide

[001963] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 -

thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[001964] 1H NMR (DMSOd6): 7.99 (1 H, br d, J = 7.5 Hz), 7.62 (1 H, m), 7.22 (1 H, m), 4, 44 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, dd, J = 11.3, 9.4 Hz), 3.81 (2 H, m), 3.40 ( 3 H, s), 3.38 (2 H, m), 3.29 (1 H, dd, J = 15.8, 9.3 Hz), 2.89 (1 H, dd, J = 15, 8, 8.0 Hz), 1.05 (6 H, d, J = 6.5 Hz). 13

[001965] C NMR (DMSOd6): 166.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 156.1, 154.9, 154.9, 129.7, 129.6, 128.3, 118.8, 118.7, 118.6, 116.6, 116.1, 116, 115.9, 113.2, 113.2, 113.1, 113.1, 49.5, 40.7, 34.7, 31.4, 31.3, 29.2, 22.3, 22.3.

[001966] Example 237: (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -1-morpholinoetan-1-one

The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige powder.

[001968] 1H NMR (DMSOd6): 7.47 (1 H, qd, J = 9.4, 4.9 Hz), 7.18 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 9.4, 11.2 Hz), 3.81 (1 H, dd, J = 11.4, 7.9 Hz), 3.75 (2 H, s), 3.59 (2 H, m), 3.56 (2 H, m), 3.49 (2 H, m), 3.45 (2 H, m), 3.36 (3 H, s), 3.28 (1 H, dd, J = 15.7, 9.2 Hz), 2.88 (1 H, dd, J = 15.8, 8.1 Hz ). 13

[001969] C NMR (DMSOd6): 166.8, 157, 156.9, 156.3, 155.3, 155.3, 149, 149, 147.6, 147.5, 147.4, 147, 4, 145.9, 145.9, 145.9, 145.8,

128.2, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 66, 66, 49.4, 45.6, 41.7, 34.8, 31.5, 29.2, 28.8.

[001970] Example 238: (S) -1- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (2- (methylsulfonyl) ethyl) cyclopropane-1-carboxamide

[001971] The compound was prepared in an analogous manner to Example 32 from (S) - (1- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) cyclopropyl) (1H-imidazol-1-yl) methanone and isolated as a light cream solid.

[001972] 1H NMR (DMSOd6): 7.84 (1 H, t, J = 5.6 Hz), 7.74 (1 H, m), 7.18 (1 H, m), 4.41 (1 H, quin, J = 8.9 Hz), 4.21 (1 H, dd, J = 9.4, 10.9 Hz), 3.81 (1 H, dd, J = 11.2, 9.1 Hz), 3.45 (2 H, q, J = 6.5 Hz), 3.37 (3 H, s), 3.24 (3 H, m), 2.98 (3 H, s), 2.98 (1 H, dd, J = 9.4, 15.4 Hz), 1.43 (1 H, m), 1.34 (1 H, m), 1.08 (1 H , m), 1.04 (1 H, m). 13

[001973] C NMR (DMSOd6): 170.7, 160.9, 160.9, 159.3, 159.3, 157.7, 157.6, 156.7, 156.1, 156, 132, 6, 132.5, 131.2, 119.1, 117.8, 117.7, 117.6, 113.8, 113.7, 113.6, 113.6, 104.1, 104, 103, 9, 103.9, 52.7, 49.2, 40.6, 35.1, 33.4, 31.5, 28.9, 19.2, 15.4, 14.8.

[001974] Example 239: (R) -N- (1,1-dioxidotetrahydro-2H-thiopyran-4-yl) - 2- (2-methyl-3-thioxo-6- (2,3,6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[001975] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige powder.

[001976] 1H NMR (DMSOd6): 8.23 (1 H, d, J = 7.6 Hz), 7.48 (1 H, qd, J = 9.4, 4.8 Hz), 7, 18 (1 H, m), 4.43 (1 H, quin, J = 8.7 Hz), 4.23 (1 H, dd, J = 9.7, 11.5 Hz), 3.95 ( 1 H, m), 3.81 (1 H, dd, J = 11.4, 7.9 Hz), 3.44 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.4 Hz), 3.23 (2 H, m), 3.06 (2 H, m), 2.90 (1 H, dd, J = 8 , 3, 15.8 Hz), 2.05 (2 H, m), 1.90 (2 H, m). 13

[001977] C NMR (DMSOd6): 167.2, 157, 156.9, 156.3, 155.4, 155.3, 149.1, 149, 149, 147.6, 147.5, 147, 5, 147.4, 147.4, 147.3, 146, 145.9, 145.9, 145.8, 128.5, 118.9, 118.8, 118.7, 118.6, 116, 5, 116.5, 116.4, 116.3, 116.3, 112, 112, 112, 111.8, 111.8, 111.8, 111.8, 49.5, 48.4, 44, 1, 34.7, 31.5, 31.2, 29.2, 29.1.

[001978] Example 240: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) acetamide

[001979] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a brown powder.

[001980] 1H NMR (DMSOd6): 7.73 (1 H, m), 7.51 (1 H, br s), 7.17 (1 H, m), 7.10 (1 H, br s ), 4.44 (1 H, quin, J = 8.7 Hz), 4.21 (1 H, dd, J = 9.4, 11.4 Hz), 3.80 (1 H, dd, J = 11.6, 7.9 Hz), 3.40 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.7, 9.4 Hz ), 2.90 (1 H, dd, J = 15.8, 8.3 Hz). 13

[001981] C NMR (DMSOd6): 169.9, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.5, 118.7, 118.5, 118.4, 116.5, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 49.5, 34.8, 31.4, 31, 29.1.

[001982] Example 241: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1 - ((S) -2- (hydroxymethyl) pyrrolidin-1-yl) ethan-1-one

[001983] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-bromo-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a brown powder.

[001984] 1H NMR (DMSOd6): 7.72 (1 H, m), 7.16 (1 H, t, J = 9.4 Hz), 5.04 (0.3 H, t, J = 5.5 Hz), 4.72 (0.7 H, t, J = 5.6 Hz), 4.44 (1 H, m), 4.22 (1 H, dd, J = 9.5, 11.1 Hz), 4.02 (0.3 H, q, J = 6.6 Hz), 3.93 (0.7 H, m), 3.79 (1.6 H, m), 3 , 64 (1.4 H, m), 3.48 (2.1 H, m), 3.43-3.36 (3.9 H, m), 3.27 (2 H, m), 2 , 86 (1 H, m), 1.85 (4 H, m). 13

[001985] C NMR (DMSOd6): 166.8, 166.7, 160.8, 160.7, 159.1, 159.1, 157.6, 157.5, 156.1, 156, 155, 9, 155.9, 132.5, 132.4, 128.3,

128.2, 118.9, 118.8, 118.8, 118.7, 116.7, 116.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 62.8, 62.8, 60.8, 58.8, 58.7, 49.6, 49.5, 46.9, 45.5, 34.8, 31, 6, 31.5, 30.6, 30, 29.2, 27.8, 26.7, 23.5, 21.4.

[001986] Example 242: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1-morpholinoetan-1-one

[001987] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white powder.

[001988] 1H NMR (DMSOd6): 7.86 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4.25 (1 H, dd, J = 11, 6, 9.2 Hz), 3.84 (1 H, dd, J = 11.6, 7.6 Hz), 3.75 (2 H, s), 3.59 (2 H, m), 3 , 55 (2 H, m), 3.49 (2 H, m), 3.45 (2 H, m), 3.36 (3 H, s), 3.30 (1 H, dd, J = 15.9, 9.3 Hz), 2.90 (1 H, dd, J = 15.8, 7.8 Hz). 13

[001989] C NMR (DMSOd6): 166.8, 156.3, 146.4, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 128, 120.5, 120.4, 120.3, 116.3, 105.9, 105.7, 105.6, 66, 66, 49.4, 45.6, 41.7, 34.9, 31.5, 29, 1, 28.8.

[001990] Example 243: 2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetra-

hydrofuran-3-yl) acetamide

[001991] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white powder.

[001992] 1H NMR (DMSOd6): 8.37 (1 H, d, J = 6.6 Hz), 7.86 (1 H, m), 4.48 (1 H, quin, J = 8, 5 Hz), 4.27-4.19 (2 H, m), 3.84 (1 H, dd, J = 11.7, 7.6 Hz), 3.77 (1 H, q, J = 7.3 Hz), 3.72 (1 H, dd, J = 8.9, 5.9 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3, 46 (1 H, br dd, J = 8.9, 3.6 Hz), 3.44 (2 H, s), 3.40 (3 H, s), 3.31 (1 H, dd, J = 9.4, 16.1 Hz), 2.93 (1 H, dd, J = 15.8, 7.9 Hz), 2.08 (1 H, m), 1.71 (1 H, m ). 13

[001993] C NMR (DMSOd6): 167.6, 156.2, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143, 6, 128.2, 120.5, 120.4, 120.3, 116.4, 105.9, 105.7, 105.6, 72.4, 66.3, 49.8, 49.4, 34.9, 32, 31.5, 31, 29.1.

[001994] Example 244: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[001995] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light beige powder.

[001996] 1H NMR (DMSOd6): 8.36 (1 H, br d, J = 6.5 Hz), 7.47 (1 H, m), 7.18 (1 H, t br), 4 , 43 (1 H, quin, J = 8.6 Hz), 4.29-4.16 (2 H, m), 3.81 (1 H, dd, J = 11.6, 8.1 Hz) , 3.77 (1 H, m), 3.72 (1 H, dd, J = 9.0, 5.9 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, dd, J = 8.9, 3.6 Hz), 3.43 (2 H, s), 3.40 (3 H, s), 3.29 (1 H , dd, J = 15.8, 9.3 Hz), 2.90 (1 H, dd, J = 15.8, 8.2 Hz), 2.08 (1 H, m), 1.71 ( 1 H, m). 13

[001997] C NMR (DMSOd6): 167.6, 157, 156.9, 156.9, 156.9, 156.2, 155.3, 155.3, 155.3, 155.3, 149, 147.5, 147.5, 147.4, 145.9, 145.8, 145.8, 128.4, 118.9, 118.8, 118.8, 118.7, 116.5, 116, 4, 116.4, 116.3, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.8, 72.3, 66.2, 49.8, 49.4, 34.7, 32, 31.5, 31.1, 29.1.

[001998] Example 245: (R) -2- (6- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N-cyclopentylacetamide

[001999] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (5-chloro-2-fluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige solid.

[002000] 1H NMR (DMSOd6): 8.08 (1 H, br d, J = 7.0 Hz), 7.46 (1 H, dd, J = 6.5, 2.5 Hz), 7 , 41 (1 H, ddd, J = 8.7, 4.3, 2.7 Hz), 7.30 (1 H, dd, J = 9.0, 10.0 Hz), 4.20 (2 H, m), 3.98 (1 H, m), 3.80 (1 H, m), 3.41 (2 H, s), 3.39 (3 H, s), 3.24 (1 H, br dd, J = 15.6, 7.5 Hz), 2.89 (1 H, br dd, J = 15.4, 7.0 Hz), 1.79 (2 H, m), 1 , 62 (2 H, m), 1.49 (2 H, m), 1.36 (2 H, m). 13

[002001] C NMR (DMSOd6): 167, 159.8, 158.2, 156.3, 130.3, 130.2, 128.9, 128.9, 128.5, 128.5, 128, 5, 128.2, 117.6, 117.4, 116.9, 50.5, 50.1, 39.8, 32.2, 32.2, 31.4, 31.2, 29.5, 23.4.

[002002] Example 246: 2 - ((R) -6- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002003] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (5-chloro-2-fluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige solid.

[002004] 1H NMR (DMSOd6): 8.37 (1 H, br d, J = 6.6 Hz), 7.46 (1 H, dd, J = 6.5, 2.6 Hz), 7 , 41 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 10.0, 8.9 Hz), 4.28-4 , 15 (3 H, m), 3.78 (2 H, m), 3.73 (1 H, dd, J = 8.9, 5.9 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.47 (1 H, dd, J = 8.9, 3.5

Hz), 3.45 (2 H, s), 3.40 (3 H, s), 3.24 (1 H, dd, J = 15.5, 7.6 Hz), 2.90 (1 H , dd, J = 15.4, 7.2 Hz), 2.08 (1 H, m), 1.71 (1 H, m). 13

[002005] C NMR (DMSOd6): 167.6, 159.8, 158.2, 156.4, 130.2, 130.1, 128.9, 128.9, 128.5, 128.5, 128.4, 117.6, 117.4, 116.7, 72.4, 66.3, 50.1, 49.8, 39.8, 32, 31.5, 31, 29.4.

[002006] Example 247: 1 - ((S) -2- (methoxymethyl) pyrrolidin-1-yl) -2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl ) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[002007] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a white powder.

[002008] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.18 (1 H, m), 4.43 (1 H, m), 4.23 (1.35 H, m ), 4.04 (0.65 H, m), 3.82 (1 H, m), 3.79 (0.7 H, m), 3.65 (1.3 H, s), 3, 53-3.37 (2.3 H, m), 3.36, 3.35 (3 H, 2 s), 3.34-3.22 (3.75 H, m), 3.21 (1 , 95 H, s), 2.92-2.84 (1 H, m), 2.0-1.73 (4 H, m). 13

[002009] C NMR (DMSOd6): 166.9, 166.6, 156.9, 156.9, 156.9, 156.9, 156.2, 156.1, 155.3, 155.3, 155.3, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145, 8, 129.5, 128.2, 128.2, 118.9, 118.9, 118.8, 118.7, 116.7, 116.5, 116.4, 116.4, 116.3, 116.3, 112, 112, 112, 111.8, 111.8, 111.8, 111.8, 73.8, 71.6, 58.5, 58.3, 56.3, 56.2, 49.4, 46.8, 45.4, 34.8, 31.5, 30.6, 29.9, 29.1, 29.1, 28.2, 27.2, 23.5, 21, 5.

[002010] Example 248: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -1 - ((S) -2- (trifluoromethyl) pyrrolidin-1-yl) etan-1-one

[002011] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[002012] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.18 (1 H, m), 5.03 (0.3 H, m), 4.76 (0.7 H , quin, J = 8.3 Hz), 4.43 (1 H, quin, J = 8.6 Hz), 4.25 (1 H, m), 3.94 (0.3 H, br d, J = 17.5 Hz), 3.83 (1 H, dd, J = 11.5, 7.8 Hz), 3.79 (1.4 H, m), 3.64 (1.7 H, m), 3.35 (3 H, s), 3.30 (1.6 H, m), 2.90 (1 H, m), 2.28-1.85 (4 H, m). 13

[002013] C NMR (DMSOd6): 168.6, 168.1, 156.9, 156.9, 156.4, 156.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.6, 147.5, 147.5, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.9, 145.8, 128, 8, 128.6, 128.5, 127, 125.1, 123.2, 118.9, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116, 115.8, 111.9, 111.8, 56.6, 56.4, 56.2, 56, 49.5, 47, 46.5, 34.8, 34.7, 31.4, 31, 4, 30.4, 29.6, 29.2, 26.2, 24.8, 23.6, 21.3.

[002014] Example 249: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) acetamide

[002015] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[002016] 1H NMR (DMSOd6): 7.62 (1 H, m), 7.51 (1 H, br s), 7.22 (1 H, m), 7.10 (1 H, br s ), 4.44 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, dd, J = 9.3, 11.3 Hz), 3.81 (1 H, dd, J = 11.5, 8.0 Hz), 3.41 (2 H, m), 3.40 (3 H, s), 3.30 (1 H, dd, J = 15.9, 9.3 Hz ), 2.91 (1 H, dd, J = 15.8, 8.3 Hz). 13

[002017] C NMR (DMSOd6): 169.9, 160.2, 160.1, 158.5, 158.5, 156.6, 156.6, 156.2, 155, 154.9, 129, 7, 129.7, 128.5, 118.7, 118.6, 118.4, 116.5, 116.1, 116.1, 116, 115.9, 113.3, 113.2, 113, 1, 113.1, 49.4, 34.8, 31.4, 31, 29.1.

[002018] Example 250: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002019] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 -

thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[002020] 1H NMR (DMSOd6): 8.37 (1 H, br d, J = 6.6 Hz), 7.61 (1 H, m), 7.21 (1 H, m), 4, 44 (1 H, quin, J = 8.5 Hz), 4.22 (2 H, m), 3.78 (2 H, m), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 9.0, 3.4 Hz), 3, 43 (2 H, m), 3.40 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.4 Hz), 2.89 (1 H, dd, J = 15.8, 8.1 Hz), 2.07 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m). 13

[002021] C NMR (DMSOd6): 167.6, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.7, 128.4, 118.8, 118.7, 118.6, 116.4, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 72.4, 66.3, 49.8, 49.5, 34.7, 32, 31.5, 31.1, 29.2.

[002022] Example 251: 2 - ((S) -6- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002023] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (5-chloro-2-fluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[002024] 1H NMR (DMSOd6): 8.37 (1 H, d, J = 6.6 Hz), 7.47 (1 H, dd, J = 6.5, 2.7 Hz), 7, 41 (1 H, ddd, J = 8.8, 4.4, 2.7 Hz), 7.30 (1 H, dd, J = 10.1, 8.8 Hz), 4.22 (3 H , m), 3.79 (2 H, m), 3.73 (1 H, dd, J = 8.9, 5.9 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (2 H, m), 3.46 (1 H, dd, J = 3.6, 9.0 Hz), 3.40 (3 H, s), 3.24 (1 H, dd, J = 15.6, 7.6 Hz), 2.90 (1 H, dd, J = 15.5, 7.3 Hz), 2.08 (1 H, m), 1 , 72 (1 H, m).

[002025] C NMR (DMSOd6): 167.6, 159.8, 158.2, 156.4, 130.2, 130.1, 128.9, 128.9, 128.5, 128.5, 128.5, 128.3, 117.6, 117.4, 116.7, 72.4, 66.3, 50.1, 49.8, 39.8, 32, 31.5, 31, 29, 4.

[002026] Example 252: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[002027] The compound was prepared analogously to Example 34 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 12) and isolated as a yellow powder.

[002028] 1H NMR (DMSOd6): 7.72 (1 H, m), 7.16 (1 H, m), 5.09 (0.6 H, m), 4.65 (0.4 H , m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 9.7, 11.2 Hz), 3.91 (1 H, m ), 3.81 (1 H, m), 3.80 (1 H, dd, J = 7.7, 11.6 Hz), 3.71 (1 H, m), 3.69 (1 H, m), 3.62 (1 H, m), 3.56 (1 H, m), 3.34 (3 H, m), 3.26 (1 H, m), 2.93 (1.8 H, m), 2.84 (1 H, m), 2.74 (1.2 H, s), 2.25-2.04 (1 H, m), 1.90-1.72 (1 H, m). 13

[002029] C NMR (DMSOd6): 168.2, 167.6, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 156.2, 156.2, 155.9, 155.8, 132.5, 132.4, 128.3, 128.1, 118.9, 118.8, 118.6, 116.5, 116.4, 113.8, 113, 8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 69.4, 69.3, 69.3, 69.2, 67.1, 67, 56.5, 56.5, 53, 49.5, 34.8, 31.5, 31.5, 31.2, 29.9, 29.8, 29.7, 29.7, 29.4, 29.4, 29.3, 29.2, 29.2, 27.6.

[002030] Example 253: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-

thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (cyanomethyl) acetamide

[002031] The compound was prepared in an analogous manner to Example 34 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic (Example 12) and isolated as a cream powder.

[002032] 1H NMR (DMSOd6): 8.78 (1 H, t, J = 5.5 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 9.7, 11.2 Hz), 4.16 (2 H, d, J = 5.6 Hz ), 3.81 (1 H, dd, J = 11.4, 8.1 Hz), 3.55 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.3 Hz), 2.90 (1 H, dd, J = 15.8, 8.2 Hz). 13

[002033] C NMR (DMSOd6): 168.6, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.5, 155.9, 155.9, 132.5, 132.4, 128.9, 118.6, 118.5, 118.4, 117.5, 115.5, 113.8, 113.8, 113.6, 113.6, 104, 1, 104.1, 103.9, 103.9, 49.5, 34.8, 31.4, 30.8, 29.1, 27.3.

[002034] Example 254: (R) -N- (1-cyanocyclopropyl) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002035] The compound was prepared in an analogous manner to Example 34 from (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6 acid, 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002036] 1H NMR (DMSOd6): 9.03 (1 H, s), 7.48 (1 H, m), 7.18 (1 H, br t, J = 9.4 Hz), 4, 43 (1 H, quin, J = 8.6 Hz), 4.24 (1 H, dd, J = 9.5, 11.3 Hz), 3.82 (1 H, dd, J = 11.4 , 8.1 Hz), 3.48 (2 H, m), 3.37 (3 H, s), 3.30 (1 H, dd, J = 9.2, 11.9 Hz), 2, 92 (1 H, dd, J = 15.8, 8.3 Hz), 1.48 (2 H, m), 1.14 (2 H, m).

[002037] 13C NMR (DMSOd6): 169.3, 156.9, 156.5, 155.3, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 128.8, 120.6, 118.8, 118.7, 118.7, 118.6, 116.5, 116, 5, 116.4, 116.3, 115.5, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 49.5, 34.7, 31, 4, 30.8, 29.1, 19.9, 15.6, 15.6.

[002038] Example 255: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[002039] The compound was prepared analogously to Example 34 from (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6 acid, 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a white powder.

[002040] 1H NMR (DMSOd6): 8.12 (1 H, br d, J = 7.3 Hz), 7.47 (1 H, m), 7.18 (1 H, br t, J = 9.6 Hz), 4.43 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 9.6, 11.3 Hz), 3.81 (1 H , dd, J = 11.5, 8.0 Hz), 3.72-3.59 (3 H, m), 3.45 (2 H, s), 3.39 (3 H, s), 3 , 36 (1 H, m), 3.29 (1 H, dd, J = 15.8, 9.3 Hz), 3.12 (1 H, m), 2.90 (1 H, dd, J = 15.7, 8.2 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.46 (2 H, m). 13

[002041] C NMR (DMSOd6): 167.3, 157, 156.9, 156.9, 156.2, 155.3, 155.3, 149.1, 149, 149, 148.9, 147, 5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.3, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 111.9, 111.8, 70.1, 67, 49.4, 45.1, 34.7, 31.5, 31.2, 29.1, 28.5, 23.8.

[002042] Example 256: (S) -6- (3-bromo-2,6-difluorophenyl) - 2-methyl-1- (2 - ((((R) -tetrahydrofuran-3-yl) hydrochloride ) ethyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[002043] The compound was prepared analogously to Example 35 from 1 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide (Example 234) and isolated as a cream powder -clear.

[002044] 1H NMR (DMSOd6): 9.20 (2 H, m), 7.74 (1 H, m), 7.18 (1

H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.22 (1 H, dd, J = 9.5, 11.1 Hz), 3.91 (2 H, m), 3.84 (1 H, s br), 3.80 (1 H, dd, J = 8.1, 11.4 Hz), 3.75 (1 H, dd, J = 6.0, 10.2 Hz), 3.64 (1 H, m), 3.47 (3 H, s), 3.40 (1 H, dd, J = 9.6, 15.9 Hz), 3.13 (2 H, br s), 3.00 (1 H, dd, J = 15.7, 8.4 Hz), 2.94 (2 H, t, J = 7.6 Hz), 2.20 ( 1 H, m), 2.03 (1 H, m). 13

[002045] C NMR (DMSOd6): 160.8, 160.8, 159.2, 159.1, 157.6, 157.6, 156.6, 156, 155.9, 132.6, 132, 5, 128.5, 118.5, 118.4, 118.3, 116.5, 113.8, 113.8, 113.7, 113.6, 104.1, 104.1, 104, 104, 68.9, 66.4, 57.5, 49.4, 43.5, 34.9, 31.4, 29.2, 28.9, 21.1.

[002046] Example 257: (R) -2-methyl-1- (2-morpholinoethyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydrohydrochloride 3H-pyrrolo [1,2-c] imidazole-3-thione

[002047] The compound was prepared analogously to Example 35 from (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1-morpholinoethane-1-one (Example 242) and isolated as a pale yellow powder.

[002048] 1H NMR (DMSOd6): 11.61 (1 H, br s), 7.88 (1 H, m), 4.51 (1 H, quin, J = 8.4 Hz), 4, 24 (1 H, dd, J = 11.3, 9.5 Hz), 3.97 (2 H, br d, J = 11.7 Hz), 3.85 (1 H, dd, J = 7, 7, 11.7 Hz), 3.82 (2 H, m), 3.48 (3 H, s), 3.47 (2 H, m), 3.43 (1 H, dd, J = 15 , 6, 8.6 Hz), 3.30 (2 H, m), 3.13-2.98 (5 H, m). 13

[002049] C NMR (DMSOd6): 156.7, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 144.8, 144.8,

144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 127.9, 120, 4, 120.3, 120.2, 116.6, 105.9, 105.8, 105.6, 63.1, 52.9, 50.8, 49.3, 34.9, 31.4, 29.2, 18.6.

[002050] Example 258: (S) -2-amino-3- (2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamido) propanoic

[002051] To a solution of pyridin-2-amine (28.9 mg, 0.307 mmol) in N, N-dimethylformamide (0.93 ml) was added N-ethyl-N-isopropylpropan-2-amine (0.10 mL, 0.557 mmol). The reaction mixture was cooled in an ice bath and 1- (bis (dimethylamino) methylene) - 1H- [1,2,3] triazolo [4,5-b] pyridine-1-ium 3-hexafluorophosphate was added (V) (HATU) (117 mg, 0.307 mmol) and (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-3,5,6 acid, 7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) acetic acid (100 mg, 0.279 mmol) in one part. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was then transferred to a separatory funnel, diluted with 30 ml of water and 40 ml of ethyl acetate. The aqueous layer was extracted twice with 40 ml of ethyl acetate. The organic layer was washed with brine, dried over MgSO4, filtered and evaporated to dryness. Chromatography gave (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrole [1, 2- c] imidazol-1-yl) -N- (pyridin-2-yl) acetamide as an off-white solid. Yield: 31 mg, 25%.

[002052] 1H NMR (DMSOd6): 10.76 (1 H, s), 8.32 (1 H, dd, J = 4.8, 1.0 Hz), 8.04 (1 H, br d , J = 8.1 Hz), 7.78 (1 H, m), 7.61 (1 H, m), 7.21 (1 H, m), 7.11 (1 H, dd, J = 7.0, 5.2 Hz), 4.46 (1 H, quin, J = 8.5 Hz), 4.24

(1 H, dd, J = 9.7, 11.1 Hz), 3.81 (1 H, dd, J = 7.9, 11.7 Hz), 3.79 (2 H, m), 3 , 44 (3 H, m), 3.31 (1 H, m), 2.92 (1 H, dd, J = 16.0, 8.1 Hz). 13

[002053] C NMR (DMSOd6): 167.7, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.4, 154.9, 154.9, 151.7, 148, 138.2, 129.7, 129.6, 128.8, 119.6, 118.8, 118.7, 118.5, 116, 116, 116, 115.9, 115, 9, 115.9, 115.8, 113.5, 113.2, 113.2, 113.1, 113, 49.5, 34.7, 31.9, 31.6, 29.2.

[002054] Example 259: (R) -2-methyl-1- (2- (pyridin-3-yl) ethyl) -6- (2,3,5,6-tetrafluorophenyl) -6,7-dihydro -2H-pyrrolo [1,2-c] imidazole-3 (5H) -thione

[002055] The compound was prepared in an analogous manner to Example 229, step 1, from (4R) -2- (3- (pyridin-3-yl) propanoyl) -4- (2,3,5,6- tert-butyl tetrafluorophenyl) pyrrolidine-1-carboxylate (Example 212, step 3) and isolated as an off-white powder.

[002056] 1H NMR (DMSOd6): 8.42 (1 H, d, J = 1.8 Hz), 8.38 (1 H, dd, J = 4.7, 1.5 Hz), 7, 84 (1 H, m), 7.62 (1 H, dt, J = 7.8, 1.8 Hz), 7.28 (1 H, dd, J = 7.7, 4.8 Hz), 4.38 (1 H, quin, J = 8.4 Hz), 4.19 (1 H, br dd, J = 11.4, 9.2 Hz), 3.79 (1 H, dd, J = 11.7, 7.4 Hz), 3.45 (3 H, s), 3.13 (1 H, dd, J = 15.7, 9.4 Hz), 2.86 (4 H, m) , 2.67 (1 H, dd, J = 15.6, 7.6 Hz). 13

[002057] C NMR (DMSOd6): 156.1, 149.7, 147.4, 146.4, 146.3, 146.2, 145.3, 145.2, 145.2, 145.2, 145.2, 145.1, 145.1, 145.1, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.6, 143.6, 143, 6, 143.6, 143.5, 143.5, 143.5, 136, 135.9, 127.1, 123.3, 120.4, 120.3, 120.2, 120.2, 105, 8, 105.7, 105.5, 49.1, 34.9, 31.2, 30.1, 29.1, 25.2.

[002058] Example 260: (R) -3- (2-methyl-6- (2,3,5,6-

tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanoic

[002059] The compound was prepared in an analogous way to Example 229, step 1, from ethyl oxoacetate and 2- (2- (dimethoxyphosphoryl) acetyl) -4- (2,3,5,6-tetrafluorophenyl) pyrrolidine- 1- (4R) -tert-butyl carboxylate (Example 212, step 3) and isolated as an off-white powder.

[002060] 1H NMR (DMSOd6): 12.33 (1 H, br s), 7.86 (1 H, m), 4.46 (1 H, quin, J = 8.5 Hz), 4, 22 (1 H, dd, J = 11.4, 9.3 Hz), 3.81 (1 H, dd, J = 11.7, 7.7 Hz), 3.44 (3 H, s), 3.38 (1 H, dd, J = 9.4, 15.2 Hz), 2.99 (1 H, dd, J = 15.7, 7.9 Hz), 2.73 (2 H, t , J = 7.3 Hz), 2.54 (2 H, t, J = 7.3 Hz). 13

[002061] C NMR (DMSOd6): 173.4, 156, 146.4, 146.3, 146.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145, 2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.5, 126.8, 120.5, 120.4, 120.4, 120.3, 105.9, 105.7, 105.6, 49.1, 34, 9, 31.4, 31.1, 29.3, 19.5.

[002062] Example 261: (R) -3- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1- (pyrrolidin-1-yl) propan-1-one

[002063] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one and isolated as an off-white powder.

[002064] 1H NMR (DMSOd6): 7.86 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11, 2, 9.5 Hz), 3.80 (1 H, dd, J = 11.6, 7.8 Hz), 3.45 (3 H, s), 3.37 (3 H, m), 3 , 25 (2 H, t, J = 6.9 Hz), 3.00 (1 H, br dd, J = 15.7, 7.9 Hz), 2.72 (2 H, m), 2, 53 (2 H, t, J = 7.7 Hz), 1.83 (2 H, quin, J = 6.7 Hz), 1.74 (2 H, m). 13

[002065] C NMR (DMSOd6): 168.9, 155.8, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 143.7, 143.7, 143, 7, 143.6, 143.6, 143.6, 143.6, 143.6, 126.7, 120.9, 120.6, 120.4, 120.3, 105.8, 105.7, 105.5, 49.1, 45.7, 45.3, 34.9, 31.5, 31.1, 29.2, 25.5, 23.9, 19.3.

[002066] Example 262: (S) -3- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) propanamide

[002067] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -3- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one and isolated as an off-white solid.

[002068] 1H NMR (DMSOd6): 7.62 (1 H, m), 7.31 (1 H, br s), 7.21 (1 H, m), 6.86 (1 H, br s ), 4.42 (1 H, quin, J = 8.7 Hz), 4.20 (1 H, dd, J = 9.3, 11.1 Hz), 3.77 (1 H, dd, J = 11.6, 7.9 Hz), 3.44 (3 H, s), 3.32 (1 H, m), 2.94 (1 H, dd, J = 15.7, 8.2 Hz ), 2.71 (2 H, t, J = 7.3 Hz), 2.35 (2 H, t, J = 7.4 Hz). 13

[002069] C NMR (DMSOd6): 172.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.8, 155, 154.9, 129, 7, 129.7, 126.8, 120.8, 118.8, 118.7, 118.6, 116.1, 116.1, 116, 115.9, 113.3, 113.2, 113, 1, 113.1, 49.2, 34.8, 32.5, 31.1, 29.4, 19.8.

[002070] Example 263: (R) -3- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) propanamide

[002071] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -3- (6- (2,6-difluorophenyl) -3-thioxo-2 , 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one and isolated as an off-white solid.

[002072] 1H NMR (DMSOd6): 7.41 (1 H, m), 7.31 (1 H, br s), 7.14 (1 H, m), 6.87 (1 H, br s ), 4.39 (1 H, quin, J = 8.8 Hz), 4.19 (1 H, dd, J = 10.6, 9.9 Hz), 3.75 (1 H, dd, J = 11.3, 8.4 Hz), 3.44 (3 H, s), 3.31 (1 H, br dd, J = 15.5, 9.3 Hz), 2.93 (1 H, dd, J = 15.6, 8.7 Hz), 2.71 (2 H, t, J = 7.3 Hz), 2.36 (2 H, t, J = 7.3 Hz). 13

[002073] C NMR (DMSOd6): 172.9, 161.6, 161.6, 160, 159.9,

155.8, 129.8, 129.8, 129.7, 126.9, 120.8, 116.6, 116.5, 116.3, 112.3, 112.2, 112.1, 112, 1, 49.2, 34.5, 32.5, 31.1, 29.6, 19.8.

[002074] Example 264: (R) -3- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1- (pyrrolidin-1-yl) propan-1-one

[002075] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -3- (6- (2,6-difluorophenyl) -3-thioxo-2 , 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one and isolated as an off-white solid.

[002076] 1H NMR (DMSOd6): 7.41 (1 H, m), 7.14 (2 H, m), 4.38 (1 H, quin, J = 8.8 Hz), 4.19 (1 H, m), 3.75 (1 H, dd, J = 11.2, 8.4 Hz), 3.45 (3 H, s), 3.37 (2 H, m), 3, 32 (1 H, m), 3.25 (2 H, t, J = 6.8 Hz), 2.95 (1 H, dd, J = 15.6, 8.7 Hz), 2.72 ( 2 H, t, J = 7.7 Hz), 2.54 (2 H, t, J = 7.5 Hz), 1.83 (2 H, m), 1.74 (2 H, m). 13

[002077] C NMR (DMSOd6): 168.9, 161.6, 161.6, 160, 159.9, 155.8, 129.8, 129.7, 129.7, 127, 120.9, 116.6, 116.5, 116.3, 112.2, 112.2, 112.1, 49.2, 45.7, 45.3, 34.4, 31.5, 31.1, 29, 4, 25.5, 23.9, 19.3.

[002078] Example 265: 3 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) propanamide

[002079] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -3- (6- (2,3,6-trifluorophenyl) -3-thioxo - 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one and isolated as a beige powder.

[002080] 1H NMR (DMSOd6): 8.09 (1 H, d, J = 6.6 Hz), 7.48 (1 H, m), 7.18 (1 H, br t, J = 9 , 5 Hz), 4.40 (1 H, quin, J = 8.6 Hz), 4.20 (1 H, dd, J = 9.4, 11.5 Hz), 4.19 (1 H, m), 3.78 (1 H, dd, J = 11.4, 7.9 Hz), 3.74-3.66 (2 H, m), 3.63 (1 H, m), 3, 44 (3 H, s), 3.38 (1 H, dd, J = 8.9, 3.6 Hz), 3.33 (1 H, m), 2.92 (1 H, dd, J = 15.6, 8.1 Hz), 2.72 (2 H, t, J = 7.3 Hz), 2.37 (2 H, t, J = 7.3 Hz), 2.03 (1 H , m), 1.62 (1 H, m). 13

[002081] C NMR (DMSOd6): 170.5, 156.9, 156.9, 155.9, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 145.8, 126.8, 120.6, 119, 118.9, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.8, 72.4, 66, 2, 49.5, 49.1, 34.7, 32.6, 32.1, 31.1, 29.5, 19.9.

[002082] Example 266: (R) -3- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -1-morpholinopropan-1-one

[002083] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -3- (6- (2,3,6-trifluorophenyl) -3-thioxo - 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one and isolated as a cream powder.

[002084] 1H NMR (DMSOd6): 7.48 (1 H, m), 7.18 (1 H, t, J = 9.4 Hz), 4.40 (1 H, quin, J = 8, 7 Hz), 4.21 (1 H, dd, J = 9.4, 11.3 Hz), 3.78 (1 H, dd, J = 11.5, 8.1 Hz), 3.51 ( 4 H, m), 3.45 (3 H, s), 3.41 (4 H, m), 3.38 (1 H, m), 2.98 (1 H, dd, J = 15.6 , 8.4 Hz), 2.72 (2 H, m), 2.63 (2 H, m). 13

[002085] C NMR (DMSOd6): 169.6, 157, 156.9, 155.8, 155.3, 155.3, 149.1, 149.1, 149, 149, 147.6, 147, 5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.8, 126.8, 120.8, 118.9, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 111.8, 66.1, 66, 49.1, 45.1, 41.5, 34.8, 31.1, 29.7, 29.3, 19.6.

[002086] Example 267: 1 - ((S) -2- (hydroxymethyl) pyrrolidin-1-yl) -3 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl ) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one

[002087] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -3- (6- (2,3,6-trifluorophenyl) -3-thioxo - 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one and isolated as a white powder.

[002088] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.18 (1 H, br t, J = 9.5 Hz), 4.92 (0.35 H, t, J = 5.7 Hz), 4.72 (0.65 H, t, J = 5.7 Hz), 4.40 (1 H, m), 4.20 (1 H, br t, J = 10, 3 Hz), 3.90 (1 H, m), 3.77 (1 H, m), 3.46 (0.65 H, m), 3.45 (3 H, s), 3.42- 3.27 (3 H, m), 3.26-3.15 (1.35 H, m), 2.97 (1 H, m), 2.71 (2 H, m), 2.68- 2.51 (2 H, m), 1.94-1.68 (4 H, m). 13

[002089] C NMR (DMSOd6): 169.6, 169.6, 156.9, 156.9, 155.8, 155.8, 155.3, 155.3, 149.1, 149, 147, 5, 147.5, 145.9, 145.9, 145.8, 145.8, 126.8, 126.8, 120.9, 120.9, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.7, 62.6, 61, 58.6, 58.5, 49.1, 46.5, 45.3, 34.8, 31.6, 31.3, 31.1, 29.3, 26.6, 23.3, 21.3, 19.2.

[002090] Example 268: (S) -3- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (pyridin-2-yl) propanamide

[002091] The compound was prepared in an analogous way to Example 168 from (S) -3- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5-acid, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanoic and isolated as an off-white solid.

[002092] 1H NMR (DMSOd6): 10.54 (1 H, s), 8.27 (1 H, ddd, J = 0.7, 1.8, 4.8 Hz), 8.01 (1 H, br d, J = 8.4 Hz), 7.75 (1 H, m), 7.57 (1 H, m), 7.12 (1 H, m), 7.08 (1 H, ddd, J = 7.3, 4.9, 1.0 Hz), 4.38 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.4, 9.4 Hz), 3.74 (1 H, dd, J = 11.7, 7.6 Hz), 3.47 (3 H, s), 3.33 (1 H, dd, J = 15, 8, 9.5 Hz), 2.90 (1 H, dd, J = 15.6, 7.7 Hz), 2.82 (2 H, m), 2.69 (2 H, m).

[002093] 13C NMR (DMSOd6): 170.8, 160, 160, 158.4, 158.3, 156.5, 156.4, 155.9, 154.8, 154.8, 151.8, 147.6, 138.4, 129.6, 129.6, 127.1, 120.3, 119.3, 118.9, 118.8, 118.7, 116, 116, 115.9, 115, 9, 113.4, 113.1, 113.1, 113, 113, 49.3, 34.7, 33.8, 31.1, 29.4, 21.6, 19.7.

[002094] Example 269: (R) -3- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (pyridin-2-yl) propanamide

[002095] The compound was prepared in an analogous way to Example 168 from (R) -3- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7- acid tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanoic and isolated as an off-white solid.

[002096] 1H NMR (DMSOd6): 10.52 (1 H, s), 8.28 (1 H, ddd, J = 0.9, 1.9, 4.9 Hz), 8.03 (1 H, br d, J = 8.2 Hz), 7.75 (1 H, m), 7.38 (1 H, m), 7.09 (1 H, ddd, J = 1.0, 4, 9, 7.4 Hz), 7.06 (2 H, m), 4.36 (1 H, quin, J = 8.7 Hz), 4.17 (1 H, dd, J = 9.7, 11.3 Hz), 3.73 (1 H, dd, J = 11.4, 8.0 Hz), 3.48 (3 H, s), 3.31 (1 H, dd, J = 15, 6, 9.4 Hz), 2.90 (1 H, dd, J = 15.7, 8.4 Hz), 2.82 (2 H, m), 2.70 (2 H, m). 13

[002097] C NMR (DMSOd6): 170.8, 161.5, 161.4, 159.9, 159.8, 155.9, 151.9, 147.8, 138.2, 129.7, 129.7, 129.6, 127.2, 120.3, 119.3, 116.6, 113.3, 112.1, 112.1, 112, 112, 49.4, 34.3, 33, 8, 31.1, 29.6, 19.7.

[002098] Example 270: (R) -N- (cyanomethyl) -3- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) propanamide

[002099] The compound was prepared in an analogous manner to Example 34 from (R) -3- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanoic and isolated as a cream powder.

[002100] 1H NMR (DMSOd6): 8.60 (1 H, t, J = 5.6 Hz), 7.47 (1 H, m), 7.17 (1 H, t, J = 9, 6 Hz), 4.41 (1 H, quin, J = 8.6 Hz), 4.19 (1 H, dd, J = 9.7, 11.3 Hz), 4.11 (2 H, m ), 3.77 (1 H, dd, J = 11.5, 8.0 Hz), 3.44 (3 H, s), 3.31 (1 H, dd, J = 9.2, 15, 5 Hz), 2.93 (1 H, dd, J = 15.6, 8.1 Hz), 2.76 (2 H, t, J = 7.3 Hz), 2.45 (2 H, t , J = 7.3 Hz). 13

[002101] C NMR (DMSOd6): 171.5, 156.9, 156.9, 156, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147, 5, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.8, 145.8, 127, 120.2, 118.9, 118.8, 118, 8, 118.7, 117.6, 116.5, 116.4, 116.4, 116.3, 112, 111.9, 111.9, 111.9, 111.8, 111.8, 111, 8, 111.7, 49.2, 34.7, 32.4, 31.1, 29.3, 27, 19.6.

[002102] Example 271: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrole [1,2- c] imidazol-1-yl) -N-cyclopentylacetamide

[002103] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3 , 5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated like a beige solid.

[002104] 1H NMR (DMSOd6): 8.12 (1 H, br d, J = 7.0 Hz), 7.64 (1 H, td, J = 8.6, 5.6 Hz), 7 , 21 (1 H, td, J = 1.0, 9.0 Hz), 4.10 (1 H, d, J = 12.0 Hz), 4.00 (1 H, sxt, J = 6, 8 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.47 (2 H, m), 3.35 (3 H, s), 2.78 (1 H, dd, J = 8.4, 4.4 Hz), 1.80 (2 H, m), 1.69 (1 H, dd, J = 8.2, 5.6 Hz), 1.63 (2 H, m), 1.50 (2 H, m), 1.39 (2 H, m), 1.25 (1 H, t, J = 4.9 Hz). 13

[002105] C NMR (DMSOd6): 167.1, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.7, 156.2, 156.1, 130.5, 130.3, 130.2, 117.1, 116.9, 116.8, 116.7, 115.8, 115.7, 115.6, 115.6, 112.9, 112, 9, 112.8, 112.8, 52.2, 50.5, 32.2, 32.2, 31.4, 31.2, 25.6, 23.4, 21.7, 21.3.

[002106] Example 272: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N-cyclopentylacetamide

[002107] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002108] 1H NMR (DMSOd6): 8.10 (1 H, d, J = 7.2 Hz), 7.58 (1 H, dd, J = 2.5, 6.7 Hz), 7, 56 (1 H, ddd, J = 6.5, 4.4, 2.2 Hz), 7.24 (1 H, dd, J = 10.1, 8.8 Hz), 4.14 (1 H , d, J = 12.0 Hz), 4.00 (1 H, sxt, J = 6.8 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.47 (2 H, m), 3.34 (3 H, s), 2.87 (1 H, dd, J = 8.4, 4.1 Hz), 1.81 (2 H, m), 1.70 ( 1 H, dd, J = 8.3, 5.4 Hz), 1.63 (2 H, m), 1.51 (2 H, m), 1.39 (2 H, m), 1.13 (1 H, t, J = 4.8 Hz). 13

[002109] C NMR (DMSOd6): 167.1, 161.8, 160.1, 156.8, 133.1, 133, 132.4, 132.3, 130.9, 129.2, 129, 1, 118, 117.8, 116.3, 116.2, 116.2, 52.4, 50.5, 32.2, 32.2, 31.5, 31.4, 31.2, 23, 4, 22.1, 20.7.

[002110] Example 273: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N-cyclopentylacetamide

[002111] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a off-white solid.

[002112] 1H NMR (DMSOd6): 8.11 (1 H, d, J = 7.2 Hz), 7.46 (1 H, dd, J = 6.5, 2.7 Hz), 7, 43 (1 H, ddd, J = 8.7, 4.3, 2.6 Hz), 7.30 (1 H, dd, J = 9.9, 8.9 Hz), 4.14 (1 H , d, J = 12.0 Hz), 4.00 (1 H, sxt, J = 6.8 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.47 (2 H, d, J = 5.6 Hz), 3.35 (3 H, s), 2.87 (1 H, dd, J = 8.3, 4.2 Hz), 1.81 (2 H, m), 1.70 (1 H, dd, J = 8.3, 5.4 Hz), 1.63 (2 H, m), 1.51 (2 H, m), 1.39 (2 H , dq, J = 12.9, 6.4 Hz), 1.13 (1 H, t, J = 4.8 Hz). 13

[002113] C NMR (DMSOd6): 167.1, 161.3, 159.6, 156.8, 130.9, 130.2, 130.2, 129.4, 129.3, 128.8, 128.7, 128.3, 117.6, 117.4, 116.3, 52.4, 50.6, 32.2, 32.2, 31.5, 31.4, 31.2, 23, 4, 22.1, 20.8.

[002114] Example 274: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrole [1,2- c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002115] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3 , 5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated like a beige solid.

[002116] 1H NMR (DMSOd6): 8.42 (1 H, d, J = 6.6 Hz), 7.64 (1 H,

td, J = 8.6, 5.8 Hz), 7.21 (1 H, dt, J = 1.0, 9.1 Hz), 4.25 (1 H, m), 4.10 (1 H, d, J = 12.0 Hz), 3.79 (2 H, m), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.68 (1 H, td, J = 8.2, 5.6 Hz), 3.50 (2 H, m), 3.48 (1 H, dd, J = 3.6, 8.9 Hz), 3.35 (3 H, s), 2.78 (1 H, dd, J = 8.4, 4.4 Hz), 2.09 (1 H, dq, J = 12.7, 7.6 Hz), 1.73 (1 H, m), 1.69 (1 H, dd, J = 8.4, 5.6 Hz), 1.26 (1 H, t, J = 4.9 Hz). 13

[002117] C NMR (DMSOd6): 167.6, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.8, 156.2, 156.1, 130.6, 130.3, 130.2, 117.1, 116.9, 116.8, 116.5, 115.8, 115.7, 115.6, 115.6, 112.9, 112, 9, 112.8, 112.8, 72.3, 66.3, 52.2, 49.8, 32.1, 31.5, 31, 25.6, 21.7, 21.2.

[002118] Example 275: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa- hydrocycloprop [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic

[002119] The compound was prepared in a manner analogous to Example 229 from (1S, 5R) -1- (5-bromo-2-fluorophenyl) -4- (3-ethoxy-3-oxopropanoyl) -3-azabicyclo [3.1.0] tert-butyl hexane-3-carboxylate and isolated as a beige solid.

[002120] 1H NMR (DMSOd6): 12.79 (1 H, br s), 7.58 (1 H, dd, J = 6.7, 2.6 Hz), 7.56 (1 H, m ), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.16 (1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.73 (2 H, m), 3.35 (3 H, s), 2.97 (1 H, dd, J = 8.4, 4.3 Hz), 1, 70 (1 H, dd, J = 8.4, 5.4 Hz), 1.13 (1 H, t, J = 4.8 Hz).

[002121] 13C NMR (DMSOd6): 170.9, 161.8, 160.2, 157.1, 133, 133, 132.4, 132.3, 131.2, 129.1, 129, 118, 117.8, 116.2, 116.2, 115.2, 52.5,

52.5, 31.5, 31.4, 29.7, 22.1, 20.5.

[002122] Example 276: acid 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) - 2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa- hydrocycloprop [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic

[002123] The compound was prepared in a manner analogous to Example 229 from (1S, 5R) -1- (5-chloro-2-fluorophenyl) -4- (3-ethoxy-3-oxopropanoyl) -3-azabicyclo [3.1.0] tert-butyl hexane-3-carboxylate and isolated as a beige solid.

[002124] 1H NMR (DMSOd6): 12.77 (1 H, m), 7.47 (1 H, dd, J = 6.5, 2.7 Hz), 7.43 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 9.9, 8.9 Hz), 4.16 (1 H, d, J = 12, 0 Hz), 3.87 (1 H, d, J = 12.0 Hz), 3.73 (2 H, m), 3.36 (3 H, s), 2.97 (1 H, dd, J = 8.4, 4.2 Hz), 1.70 (1 H, dd, J = 8.4, 5.4 Hz), 1.13 (1 H, t, J = 4.8 Hz). 13

[002125] C NMR (DMSOd6): 170.9, 161.3, 159.6, 157.1, 131.2, 130.2, 130.1, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 115.2, 52.4, 52.4, 31.6, 31.4, 29.7, 22.1, 20, 6.

[002126] Example 277: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[002127] The compound was prepared analogously to Example 34 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3 acid, 5.5a, 6.6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic and isolated as an off-white solid.

[002128] 1H NMR (DMSOd6): 8.15 (1 H, br d, J = 7.3 Hz), 7.58 (1 H, dd, J = 6.7, 2.6 Hz), 7 , 56 (1 H, ddd, J = 2.5, 4.5, 8.5 Hz), 7.24 (1 H, dd, J = 8.8, 10.1 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.2 Hz), 3.73-3.67 (2 H, m), 3.65 (1 H, m), 3.52 (2 H, m), 3.37 (1 H, m), 3.14 (1 H, m), 3.34 (3 H, s), 2.88 (1 H, dd, J = 8.4, 4.3 Hz), 1.83 (1 H, m), 1.70 (1 H, dd, J = 8.3, 5.4 Hz), 1.69 (1 H, m), 1.49 (2 H, m), 1.12 (1 H, t, J = 4.8 Hz). 13

[002129] C NMR (DMSOd6): 167.4, 161.8, 160.1, 156.8, 133.1, 133, 132.4, 132.3, 130.9, 129.2, 129, 1, 118, 117.8, 116.2, 116.2, 70.1, 67, 52.4, 45.2, 31.5, 31.4, 31.1, 28.6, 23.9, 22.1, 20.7.

[002130] Example 278: 2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[002131] The compound was prepared analogously to Example 34 from (R) -2- (2-methyl-3-thioxo-6- (2,3,5,6-tetrafluorophenyl) - 2,5 acid, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white powder.

[002132] 1H NMR (DMSOd6): 8.13 (1 H, br d, J = 7.3 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8 , 5 Hz), 4.24 (1 H, dd, J = 11.4, 9.2 Hz), 3.84 (1 H, dd, J = 11.7, 7.7 Hz), 3.72 -3.59 (3 H, m), 3.45 (2 H, s), 3.40 (3 H, s), 3.36 (1 H, m), 3.30 (1 H, dd, J = 9.4, 16.0 Hz), 3.12 (1 H, m), 2.92 (1 H, dd, J = 15.9, 7.8 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.46 (2 H, m). 13

[002133] C NMR (DMSOd6): 167.3, 156.2, 146.4, 146.3, 146.3, 145.4, 145.3, 145.3, 145.3, 145.2, 144.9, 144.8, 144.8, 144.7, 144.7, 144.7, 144.7, 144.6, 144.6, 144.6, 143.8, 143.7, 143, 7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.2, 120.5, 120.4, 120.3, 116.5, 105.9, 105.7, 105.6, 70.1, 67, 49.4, 45.1, 34.9, 31.5, 31.2, 29.1, 28.5, 23.8.

[002134] Example 279: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002135] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002136] 1H NMR (DMSOd6): 8.40 (1 H, d, J = 6.6 Hz), 7.58 (1 H, dd, J = 6.6, 2.5 Hz), 7, 56 (1 H, ddd, J = 8.6, 4.5, 2.6 Hz), 7.24 (1 H, dd, J = 10.1, 8.8 Hz), 4.26 (1 H , m), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d,

J = 12.0 Hz), 3.79 (1 H, q, J = 7.3 Hz), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.68 ( 1 H, td, J = 8.2, 5.6 Hz), 3.56-3.45 (3 H, m), 3.35 (3 H, s), 2.88 (1 H, dd, J = 8.4, 4.3 Hz), 2.10 (1 H, m), 1.74 (1 H, m), 1.70 (1 H, dd, J = 8.4, 5.3 Hz), 1.13 (1 H, t, J = 4.8 Hz). 13

[002137] C NMR (DMSOd6): 167.7, 161.8, 160.1, 156.8, 133.1, 133, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 116.1, 72.3, 66.3, 52.4, 49.8, 32.1, 31.5, 31.4, 31, 22, 1, 20.7.

[002138] Example 280: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002139] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002140] 1H NMR (DMSOd6): 7.59 (1 H, dd, J = 6.7, 2.6 Hz), 7.56 (1 H, ddd, J = 8.7, 4.4, 2.6 Hz), 7.53 (1 H, br s), 7.24 (1 H, dd, J = 10.0, 8.8 Hz), 7.14 (1 H, br s), 4 , 14 (1 H, d, J = 11.9 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.49 (2 H, m), 3.35 (3 H, s), 2.93 (1 H, dd, J = 8.4, 4.1 Hz), 1.67 (1 H, dd, J = 8.3, 5.4 Hz), 1.17 (1 H, t, J = 4.8 Hz). 13

[002141] C NMR (DMSOd6): 170, 161.8, 160.1, 156.8, 133, 133, 132.3, 132.3, 131.1, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 52.5, 52.4, 31.5, 31.4, 30.9, 22.1, 20.6.

[002142] Example 281: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrole [1,2-

c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002143] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002144] 1H NMR (DMSOd6): 8.41 (1 H, br d, J = 6.6 Hz), 7.47 (1 H, dd, J = 6.6, 2.6 Hz), 7 , 43 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 8.9, 9.8 Hz), 4.26 (1 H, m), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.79 (1 H, q, J = 7.5 Hz), 3.74 (1 H, dd, J = 8.9, 6.0 Hz), 3.68 (1 H, m), 3.56-3.46 (3 H, m) , 3.35 (3 H, s), 2.88 (1 H, dd, J = 8.3, 4.2 Hz), 2.10 (1 H, dq, J = 12.7, 7.6 Hz), 1.74 (1 H, m), 1.70 (1 H, dd, J = 8.3, 5.4 Hz), 1.13 (1 H, t, J = 4.8 Hz) . 13

[002145] C NMR (DMSOd6): 167.7, 161.3, 159.6, 156.8, 131, 130.2, 130.2, 129.4, 129.3, 128.8, 128, 6, 128.3, 128.3, 117.6, 117.4, 116.1, 72.3, 66.3, 52.4, 49.8, 32.1, 31.6, 31.5, 31, 22.1, 20.7.

[002146] Example 282: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002147] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a off-white solid.

[002148] 1H NMR (DMSOd6): 7.53 (1 H, br s), 7.48 (1 H, dd, J = 6.5, 2.6 Hz), 7.43 (1 H, ddd , J = 8.7, 4.3, 2.6 Hz), 7.30 (1 H, dd, J = 9.8, 9.0 Hz), 7.14 (1 H, br s), 4 , 14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.49 (2 H, m), 3.35 (3 H, s), 2.93 (1 H, dd, J = 8.4, 4.1 Hz), 1.68 (1 H, dd, J = 8.4, 5.3 Hz), 1.17 (1 H, m). 13

[002149] C NMR (DMSOd6): 170, 161.3, 159.6, 156.8, 131.1, 130.2, 130.2, 129.4, 129.3, 128.8, 128, 7, 128.3, 128.3, 117.6, 117.4, 116.2, 52.4, 31.5, 31.4, 30.9, 22.1, 20.6.

[002150] Example 283: 1 - ((S) -2- (methoxymethyl) pyrrolidin-1-yl) -2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[002151] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white powder.

[002152] 1H NMR (DMSOd6): 7.86 (1 H, m), 4.48 (1 H, quin, J = 8.4 Hz), 4.29-4.18 (1.35 H, m), 4.04 (0.65 H, m), 3.88-3.82 (1 H, m), 3.79 (0.65 H, m), 3.66 (1.35 H, s), 3.54-3.41 (1.65 H, m), 3.40 (1 H, m), 3.37, 3.36 (3 H, 2 s), 3.32-3, 23 (3.4 H, m), 3.22 (1.95 H, s), 2.91 (1 H, m), 2.0 - 1.73 (4 H, m). 13

[002153] C NMR (DMSOd6): 166.9, 166.6, 156.3, 156.1, 146.4, 146.3, 146.3, 146.3, 146.2, 146.2, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144.6, 143.7, 143.7, 143, 6, 143.6, 128.1, 128, 120.5, 120.4, 120.3, 116.8, 116.3, 105.9, 105.7, 105.6, 73.8, 71, 6, 58.5, 58.3, 56.3, 56.2, 49.4, 46.8, 45.4, 34.9, 31.5, 30.6, 29.8, 29, 29, 28.2, 27.1, 23.5, 21.5.

[002154] Example 284: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N-isopropylacetamide

[002155] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a off-white solid.

[002156] 1H NMR (DMSOd6): 8.01 (1 H, br d, J = 7.6 Hz), 7.58 (1 H, dd, J = 6.7, 2.6 Hz), 7 , 57 (1 H, ddd, J = 2.6, 4.5, 8.5 Hz), 7.24 (1 H, dd,

J = 10.1, 8.9 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.90-3.80 (2 H, m), 3.46 (2 H, m), 3.35 (3 H, s), 2.88 (1 H, dd, J = 8.3, 4.2 Hz), 1.70 (1 H, dd, J = 8.3, 5 , 4 Hz), 1.13 (1 H, t, J = 4.8 Hz), 1.07 (6 H, d, J = 6.6 Hz). 13

[002157] C NMR (DMSOd6): 166.7, 161.8, 160.1, 156.8, 133.1, 133, 132.3, 132.3, 130.9, 129.2, 129, 1, 118, 117.8, 116.3, 116.2, 116.2, 52.4, 52.4, 40.7, 31.5, 31.4, 31.2, 22.3, 22, 3, 22, 20.7.

[002158] Example 285: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (1,3,4-thiadiazol-2-yl) acetamide

[002159] The compound was prepared analogously to Example 258 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5-acid, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white solid.

[002160] 1H NMR (DMSOd6): 9.17 (1 H, s), 7.61 (1 H, m), 7.21 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 11.4, 9.5 Hz), 3.90 (2 H, m), 3.82 (1 H, dd, J = 11 , 6, 7.8 Hz), 3.42 (3 H, s), 3.31 (1 H, m), 2.92 (1 H, dd, J = 16.0, 8.1 Hz). 13

[002161] C NMR (DMSOd6): 167.6, 160.2, 160.1, 158.7, 158.5, 158.5, 156.6, 156.5, 154.9, 154.9, 148.9, 129.7, 129.7, 129.3, 118.8, 118.6, 118.5, 116.1, 116.1, 116, 115.9, 114.7, 113.3, 113.2, 113.1, 113.1, 49.6, 34.7, 31.6, 30.9, 29.1.

[002162] Example 286: (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (oxazol-2-

il) acetamide

[002163] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a light cream powder.

[002164] 1H NMR (DMSOd6): 11.45 (1 H, br s), 7.87 (1 H, s), 7.47 (1 H, m), 7.18 (1 H, m) , 7.10 (1 H, s), 4.44 (1 H, quin, J = 8.6 Hz), 4.25 (1 H, dd, J = 9.6, 11.2 Hz), 3 , 83 (1 H, dd, J = 11.5, 8.0 Hz), 3.79 (2 H, br s), 3.41 (3 H, s), 3.33 (1 H, m) , 2.94 (1 H, dd, J = 15.8, 8.2 Hz).

[002165] 13C NMR (DMSOd6): 166.7, 157, 156.9, 156.5, 155.3, 155.3, 155.3, 153, 149.1, 149, 149, 149, 148, 9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 136.2, 129.1, 126.7, 118.8, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 115, 1, 112, 112, 112, 111.8, 111.8, 111.8, 49.5, 34.7, 31.6, 31.4, 29.1.

[002166] Example 287: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H hydrochloride -pyrrolo [1,2- c] imidazol-1-yl) -N- (pyridin-4-yl) acetamide

[002167] The compound was prepared analogously to Example 168 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5-acid, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white solid.

[002168] 1H NMR (DMSOd6): 12.16 (1 H, s), 8.71 (2 H, d, J = 7.2 Hz), 8.13 (2 H, d, J = 7, 2 Hz), 7.62 (1 H, m), 7.22 (1 H, m), 4.46 (1 H, quin, J = 8.5 Hz), 4.25 (1 H, dd, J = 9.6, 11.3 Hz), 3.97 (2 H, m), 3.83 (1 H, dd, J = 11.6, 7.8 Hz), 3.45 (3 H, s), 3.37 (1 H, dd, J = 9.3, 16.0 Hz), 2.95 (1 H, dd, J = 16.0, 7.9 Hz). 13

[002169] C NMR (DMSOd6): 169.6, 160.1, 160.1, 158.5, 158.4, 156.6, 156.6, 156.5, 154.9, 154.9, 152.6, 142.6, 129.7, 129.7, 129.4, 118.8, 118.7, 118.5, 116.1, 116, 115.9, 115.9, 114.7, 114.4, 113.3, 113.2, 113.1, 113.1, 49.6, 34.7, 32.5, 31.7, 29.3.

[002170] Example 288: 3 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) propanamide

[002171] The compound was prepared in an analogous manner to Example 34 from (R) -3- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanoic and isolated as an off-white solid.

[002172] 1H NMR (DMSOd6): 7.82 (1 H, d, J = 7.5 Hz), 7.48 (1 H, m), 7.18 (1 H, br t, J = 9 , 4 Hz), 4.40 (1 H, quin, J = 8.6 Hz), 4.20 (1 H, dd, J = 11.2, 9.3 Hz), 3.78 (1 H, dd, J = 11.6, 7.9 Hz), 3.66-3.58 (3 H, m), 3.44 (3 H, m), 3.34 (1 H, m), 3, 32 (1 H, m), 3.04 (1 H, m), 2.92 (1 H, dd, J = 15.7, 8.2 Hz), 2.72 (2 H, t, J = 7.3 Hz), 2.38 (2 H, m), 1.74 (1 H, m), 1.61 (1 H, m), 1.40 (2 H, m). 13

[002173] C NMR (DMSOd6): 170.3, 156.9, 156.9, 156.9, 155.9, 155.5, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.8, 145.8, 126, 8, 120.6, 118.9, 118.9, 118.8, 118.7, 116.5, 116.5, 116.4, 116.3, 112, 112, 112, 111.9, 111, 8, 111.8, 111.8, 111.8, 70.2, 67, 49.1, 44.8, 34.8, 32.6, 31.1, 29.5, 28.6, 23, 8, 19.9.

[002174] Example 289: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[002175] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a white powder.

[002176] 1H NMR (DMSOd6): 8.37 (1 H, d, J = 6.6 Hz), 7.47 (1 H, m), 7.18 (1 H, br t, J = 9 , 6 Hz), 4.43 (1 H, quin, J = 8.7 Hz), 4.23 (2 H, m), 3.81 (1 H, dd, J = 10.9, 7.4 Hz), 3.77 (1 H, m), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.2, 5 , 6 Hz), 3.46 (1 H, dd, J = 8.9, 3.7 Hz), 3.43 (2 H, m), 3.40 (3 H, s), 3.29 ( 1 H, dd, J = 15.7, 9.4 Hz), 2.90 (1 H, dd, J = 15.8, 8.3 Hz), 2.08 (1 H, m), 1, 71 (1 H, m). 13

[002177] C NMR (DMSOd6): 167.6, 157, 156.9, 156.9, 156.9, 156.2, 155.3, 155.3, 149.1, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.4, 145.9, 145.9, 145.9, 145.8, 128.4, 118.9, 118.8, 118, 7, 118.6, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 72, 4, 66.3, 49.8, 49.4, 34.7, 32, 31.5, 31.1, 29.1.

[002178] Example 290: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (pyridin-3-ylmethyl) acetamide

[002179] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002180] 1H NMR (DMSOd6): 8.67 (1 H, br t, J = 5.9 Hz), 8.50 (1 H, d, J = 1.8 Hz), 8.44 (1 H, dd, J = 4.7, 1.3 Hz), 7.70 (1 H, m), 7.62 (1 H, m), 7.37 (1 H, dd, J = 7.8 , 4.8 Hz), 7.22 (1 H, m), 4.41 (1 H, quin, J = 8.6 Hz), 4.31 (2 H, m), 4.22 (1 H , dd, J = 9.5, 11.0 Hz), 3.80 (1 H, dd, J =

11.5, 8.0 Hz), 3.52 (2 H, m), 3.38 (3 H, m), 3.22 (1 H, dd, J = 15.8, 9.3 Hz) , 2.82 (1 H, dd, J = 15.8, 8.3 Hz). 13

[002181] C NMR (DMSOd6): 168, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 148, 4, 147.7, 135.7, 135, 129.7, 129.7, 128.5, 123.6, 118.6, 118.5, 118.4, 116.1, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 49.4, 39.8, 34.7, 31.4, 31.2, 29.1.

[002182] Example 291: (S) -N- (benzo [d] [1,3] dioxol-5-ylmethyl) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl- 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002183] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002184] 1H NMR (DMSOd6): 8.52 (1 H, t, J = 5.9 Hz), 7.62 (1 H, m), 7.22 (1 H, m), 6.81 (2 H, m), 6.72 (1 H, m), 5.95 (2 H, m), 4.41 (1 H, quin, J = 8.7 Hz), 4.21 (1 H , dd, J = 9.4, 11.4 Hz), 4.17 (2 H, m), 3.79 (1 H, dd, J = 11.6, 8.1 Hz), 3.49 ( 2 H, m), 3.39 (3 H, s), 3.22 (1 H, dd, J = 15.8, 9.3 Hz), 2.83 (1 H, dd, J = 15, 8, 8.2 Hz). 13

[002185] C NMR (DMSOd6): 167.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 147.2, 146.1, 133, 129.7, 129.7, 128.4, 120.6, 118.6, 118.5, 118.4, 116.3, 116.1, 116, 115, 9, 115.9, 113.2, 113.2, 113.1, 113.1, 108.1, 108, 100.8, 49.4, 42.2, 34.7, 31.4, 31, 3, 29.1.

[002186] Example 292: 1 - ((R) -3-fluoropyrrolidin-1-yl) -2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2 , 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-

1-il) etan-1-one

[002187] The compound was prepared in an analogous way to Example 34 from (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a white solid.

[002188] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.18 (1 H, m), 5.36 (1 H, mt, J = 52 Hz), 4.44 (1 H, m), 4.24 (1 H, m), 3.87-3.52 (6 H, m), 3.51- 3.40 (0.5 H, m), 3.37 (3 H, s), 3.31 - 3.24 (1.5 H, m), 2.88 (1 H, m), 2.29 - 1.92 (2 H, m). 13

[002189] C NMR (DMSOd6): 166.6, 166.5, 156.9, 156.9, 156.3, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.3, 128, 2, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.1, 116, 112, 111.8, 94.2, 93, 92.6, 91.4, 62.8, 54.9, 52.8, 52.6, 52.4, 52.3, 49.4, 43.8, 43.5, 34.7, 32.1, 32, 31.5, 30.5, 30.4, 30.2, 29.1, 29.1.

[002190] Example 293: (R) -N- (2-hydroxyethyl) -N-methyl-2- (2-methyl-3-thioxo- 6- (2,3,6-trifluorophenyl) -2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002191] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002192] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.18 (1 H, br t, J = 9.7 Hz), 4.93 (0.6 H, t, J = 5.3 Hz), 4.67 (0.4 H, t, J = 5.4 Hz), 4.43 (1 H, m), 4.24 (1 H, br t, J = 10, 3 Hz), 3.81 (1 H, dd, J = 11.6, 8.1 Hz), 3.79 (1.2 H, s), 3.71 (0.8 H, s), 3 , 56 (1.2 H, q, J = 5.3 Hz), 3.47 (0.8 H, q, J = 5.8 Hz), 3.42 (1.2 H, m), 3 , 35 (0.8 H, m), 3.35 (3 H, s), 3.32-3.21 (1 H, m), 3.06 (1.2 H, s), 2.88 (1 H, m), 2.84 (1.8 H, s). 13

[002193] C NMR (DMSOd6): 168.3, 167.9, 157, 156.9, 156.2, 156.1, 155.3, 155.3, 155.3, 155.3, 149, 1, 149, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.4, 147.3, 145.9, 145, 9, 145.9, 145.8, 128.2, 128.1, 118.9, 118.9, 118.8, 118.8, 118.8, 118.7, 118.7, 118.6, 116.9, 116.6, 116.5, 116.4, 116.4, 116.3, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111, 8, 58.5, 58.3, 51.4, 50, 49.4, 36.3, 34.7, 33.2, 31.5, 29.4, 29.1, 29, 29.

[002194] Example 294: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-cyclohexylacetamide

[002195] The compound was prepared in a manner analogous to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002196] 1H NMR (DMSOd6): 8.01 (1 H, d, J = 7.8 Hz), 7.58 (1 H, dd, J = 2.5, 8.9 Hz), 7, 55 (1 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.85 ( 1 H, d, J = 12.0 Hz), 3.55 (1 H, m), 3.47 (2 H, m), 3.34 (3 H, s), 2.87 (1 H, dd, J = 8.3, 4.2 Hz), 1.75 (2 H, m), 1.70 (1 H, dd, J = 5.5, 8.4 Hz), 1.67 (2 H, m), 1.55 (1 H, m), 1.25 (2 H, m), 1.21-1.08 (4 H, m). 13

[002197] C NMR (DMSOd6): 166.6, 161.8, 160.1, 156.8, 133.1, 133, 132.4, 132.3, 130.9, 129.2, 129, 1, 118, 117.8, 116.3, 116.2, 116.2, 52.4, 52.4, 47.8, 32.4, 32.3, 31.5, 31.4, 31, 2, 25.2, 24.5, 22, 20.7.

[002198] Example 295: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((S) - tetrahydrofuran-3-yl) acetamide

[002199] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white powder.

[002200] 1H NMR (DMSOd6): 8.37 (1 H, br d, J = 6.6 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8 , 5 Hz), 4.23 (2 H, m), 3.84 (1 H, dd, J = 11.6, 7.6 Hz), 3.78 (1 H, q, J = 7.3 Hz), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, dd, J = 9.0, 3.6 Hz), 3.43 (2 H, m), 3.40 (3 H, m), 3.31 (1 H, dd, J = 9.2 , 15.8 Hz), 2.93 (1 H, dd, J = 16.0, 7.9 Hz), 2.08 (1 H, m), 1.71 (1 H, m). 13

[002201] C NMR (DMSOd6): 167.6, 156.2, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.7,

144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.2, 120.4, 116.4, 105.9, 105, 7, 105.6, 72.4, 66.3, 49.8, 49.4, 34.9, 32, 31.5, 31.1, 29.1.

[002202] Example 296: 1 - ((S) -2- (fluoromethyl) pyrrolidin-1-yl) -2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl ) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[002203] The compound was prepared in an analogous manner to Example 34 from (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a white solid.

[002204] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.18 (1 H, br t, J = 9.6 Hz), 4.53-4.30 (3.25 H , m), 4.24 (1 H, m), 4.13 (0.75 H, m), 3.82 (1.25 H, m), 3.70 (1.5 H, s), 3.70 (0.25 H, m), 3.56-3.42 (1.75 H, m), 3.37, 3.36 (3 H, 2 s), 3.32-3.24 (1.25 H, m), 2.89 (1 H, m), 2.05-1.77 (4 H, m). 13

[002205] C NMR (DMSOd6): 167.1, 167, 156.9, 156.9, 156.3, 156.2, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.3, 147.3, 145.9, 145.9, 145.9, 145.8, 128.3, 128.3, 118.9, 118.8, 118.8, 118.7, 116.5, 116.5, 116.4, 116.4, 116.3, 116.1, 112, 112, 111.9, 111, 9, 111.8, 111.8, 111.8, 111.8, 84.6, 83.5, 83.1, 82, 56.4, 56.3, 56.2, 56.1, 49, 5, 46.9, 45.7, 34.8, 34.7, 31.5, 30.5, 29.7, 29.7, 29.1, 27.3, 27.3, 26.5, 26.5, 23.8, 21.5.

[002206] Example 297: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002207] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white powder.

[002208] 1H NMR (DMSOd6): 8.12 (1 H, d, J = 7.6 Hz), 7.86 (1 H, m), 4.48 (1 H, quin, J = 8, 5 Hz), 4.24 (1 H, dd, J = 11.6, 9.2 Hz), 3.84 (1 H, dd, J = 7.6, 11.7 Hz), 3.81 ( 2 H, m), 3.75 (1 H, m), 3.42 (2 H, s), 3.40 (3 H, s), 3.36-3.28 (3 H, m), 2.93 (1 H, dd, J = 15.8, 7.9 Hz), 1.69 (2 H, m), 1.38 (2 H, m). 13

[002209] C NMR (DMSOd6): 166.8, 156.2, 146.4, 146.3, 146.3, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 143.7, 143.7, 143, 6, 143.6, 143.6, 143.6, 128.2, 120.5, 120.4, 120.3, 116.5, 105.9, 105.7, 105.6, 65.8, 49.4, 45.2, 34.9, 32.4, 32.4, 31.5, 31.3, 29.1.

[002210] Example 298: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N- (2,2,2-trifluoroethyl) acetamide

[002211] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002212] 1H NMR (DMSOd6): 8.80 (1 H, t, J = 6.3 Hz), 7.58 (1 H, dd, J = 2.5, 6.7 Hz), 7, 56 (1 H, ddd, J = 6.5, 4.4, 2.2 Hz), 7.24 (1 H, dd, J = 10.0, 8.8 Hz), 4.15 (1 H , d, J = 12.0 Hz), 3.95 (2 H, m), 3.86 (1 H, d, J = 12.0 Hz), 3.64 (2 H, m), 3, 34 (3 H, s), 2.91 (1 H, dd, J = 8.4, 4.3 Hz), 1.69 (1 H, dd, J = 8.3, 5.4 Hz), 1.15 (1 H, t, J = 4.8 Hz).

[002213] 13C NMR (DMSOd6): 168.9, 161.8, 160.1, 157.1, 133, 133, 132.4, 132.3, 131.4, 129.1, 129, 127, 5, 125.6, 123.8, 121.9, 118, 117.8, 116.2, 116.2, 115.3, 52.5, 52.4, 31.5, 31.3, 30, 8, 22.8, 22, 20.6.

[002214] Example 299: (R) -2- (2-methyl-6- (2,3,6-trifluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002215] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo -

3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a white powder.

[002216] 1H NMR (DMSOd6): 8.12 (1 H, d, J = 7.6 Hz), 7.47 (1 H, m), 7.18 (1 H, br t, J = 9 , 6 Hz), 4.43 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 9.7, 11.3 Hz), 3.79 (3 H, m), 3.75 (1 H, m), 3.42 (2 H, m), 3.40 (3 H, s), 3.33 (2 H, m), 3.29 (1 H, dd, J = 9.3, 15.7 Hz), 2.90 (1 H, dd, J = 15.7, 8.2 Hz), 1.69 (2 H, md), 1.38 (2 H, mq). 13

[002217] C NMR (DMSOd6): 166.8, 156.9, 156.9, 156.2, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 145.8, 128, 3, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.8, 65.8, 49.4, 45.2, 34.7, 32.4, 31.5, 31.3, 29.2.

[002218] Example 300: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N- (2,2,2-trifluoroethyl) acetamide

[002219] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002220] 1H NMR (DMSOd6): 8.80 (1 H, t, J = 6.3 Hz), 7.46 (1 H, dd, J = 6.5, 2.7 Hz), 7, 43 (1 H, ddd, J = 8.8, 4.4, 2.7 Hz), 7.30 (1 H, dd, J = 9.9, 8.7 Hz), 4.15 (1 H , d, J = 12.0 Hz), 3.95 (2 H, m), 3.86 (1 H, d, J = 12.0 Hz),

3.64 (2 H, m), 3.34 (3 H, s), 2.91 (1 H, dd, J = 8.4, 4.3 Hz), 1.69 (1 H, dd, J = 8.4, 5.3 Hz), 1.16 (1 H, t, J = 4.8 Hz). 13

[002221] C NMR (DMSOd6): 168.9, 161.3, 159.6, 157.1, 131.4, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 127.5, 125.6, 123.8, 121.9, 117.6, 117.4, 115.3, 52.4, 52.4, 39, 9, 31.5, 31.3, 30.8, 22, 20.6.

[002222] Example 301: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[002223] The compound was prepared analogously to Example 34 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3 acid, 5.5a, 6.6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a beige solid.

[002224] 1H NMR (DMSOd6): 8.15 (1 H, d, J = 7.3 Hz), 7.47 (1 H, dd, J = 6.5, 2.6 Hz), 7, 43 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 10.0, 8.8 Hz), 4.14 (1 H , d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.70 (2 H, m), 3.65 (1 H, m), 3, 52 (2 H, m), 3.38 (1 H, m), 3.34 (3 H, s), 3.14 (1 H, m), 2.88 (1 H, dd, J = 8 , 4, 4.1 Hz), 1.83 (1 H, m), 1.70 (1 H, dd, J = 5.5, 8.4 Hz), 1.68 (1 H, m), 1.49 (2 H, m), 1.13 (1 H, t, J = 4.8 Hz). 13

[002225] C NMR (DMSOd6): 167.4, 161.3, 159.6, 156.8, 130.9, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116.2, 70.1, 67, 52.4, 52.4, 45.2, 31.5, 31.4, 31.1, 28.6, 23.9, 22.1, 20.7.

[002226] Example 302: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-cyclohexylacetamide

[002227] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002228] 1H NMR (DMSOd6): 8.01 (1 H, d, J = 7.8 Hz), 7.46 (1 H, dd, J = 6.5, 2.6 Hz), 7, 43 (1 H, ddd, J = 8.7, 4.3, 2.7 Hz), 7.30 (1 H, dd, J = 9.9, 8.9 Hz), 4.14 (1 H , d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.55 (1 H, m), 3.48 (2 H, m), 3, 35 (3 H, s), 2.88 (1 H, dd, J = 8.3, 4.2 Hz), 1.75 (2 H, br d, J = 11.2 Hz), 1.70 (1 H, dd, J = 5.4, 8.3 Hz), 1.69 (2 H, m), 1.55 (1 H, m), 1.25 (2 H, m), 1, 15 (4 H, m).

[002229] 166.6, 161.3, 159.6, 156.8, 130.9, 130.2, 130.2, 129.4, 129.3, 128.8, 128.6, 128.3 , 128.3, 117.6, 117.4, 116.3, 52.4, 52.4, 47.8, 32.4, 32.3, 31.5, 31.4, 31.2, 25 , 2, 24.5, 22, 20.8.

[002230] Example 303: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N-isopropylacetamide

[002231] The compound was prepared in an analogous way to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a gray solid.

[002232] 1H NMR (DMSOd6): 8.02 (1 H, d, J = 7.6 Hz), 7.47 (1 H, dd, J = 6.5, 2.7 Hz), 7, 43 (1 H, ddd, J = 8.7, 4.4, 2.7 Hz), 7.30 (1 H, dd, J = 10.0, 8.8 Hz), 4.14 (1 H , d, J = 12.0 Hz), 3.85 (2 H, m), 3.46 (2 H, d, J = 7.3 Hz), 3.35 (3 H, s), 2, 88 (1 H, dd, J = 8.4, 4.2 Hz), 1.70 (1 H, dd, J = 8.4, 5.4 Hz), 1.14 (1 H, t, J = 4.8 Hz), 1.07 (6 H, d, J = 6.6 Hz). 13

[002233] C NMR (DMSOd6): 166.7, 161.3, 159.6, 156.8, 130.9, 130.2, 130.2, 129.4, 129.3, 128.8, 128.7, 128.3, 128.3, 117.6, 117.4, 116.3, 52.4, 52.4, 40.7, 31.5, 31.4, 31.2, 22, 3, 22.3, 22.1, 20.7.

[002234] Example 304: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N- (cyanomethyl) acetamide

[002235] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002236] 1H NMR (DMSOd6): 8.77 (1 H, t, J = 5.6 Hz), 7.47 (1 H, dd, J = 6.5, 2.6 Hz), 7, 43 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 9.8, 8.9 Hz), 4.18 (2 H , d, J = 5.6 Hz), 4.16 (1 H, d, J = 12.0 Hz), 3.87 (1 H, d, J = 12.0 Hz), 3.63 (2 H, m), 3.34 (3 H, s), 2.92 (1 H, dd, J = 8.4, 4.3 Hz), 1.68 (1 H, dd, J = 8.3 , 5.4 Hz), 1.18 (1 H, t, J = 4.8 Hz). 13

[002237] C NMR (DMSOd6): 168.7, 161.2, 159.6, 157.1, 131.4, 130.2, 130.1, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.5, 117.4, 115.1, 52.4, 31.6, 31.3, 30.7, 27.3, 22, 1, 20.6.

[002238] Example 305: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N- (cyanomethyl) acetamide

[002239] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a white solid.

[002240] 1H NMR (DMSOd6): 8.77 (1 H, t, J = 5.6 Hz), 7.59 (1 H, dd, J = 6.7, 2.6 Hz), 7, 56 (1 H, ddd, J = 8.6, 4.5, 2.6 Hz), 7.24 (1 H, dd, J = 8.7, 10.2 Hz), 4.18 (2 H , d, J = 5.6 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.63 (2 H, m), 3.34 (3 H, s), 2.92 (1 H, dd, J = 8.4, 4.2 Hz), 1.68 (1 H, dd, J = 8.4 , 5.4 Hz), 1.18 (1 H, t, J = 4.8 Hz).

[002241] 13C NMR (DMSOd6): 168.7, 161.8, 160.1, 157.1, 133, 133, 132.4, 132.3, 131.4, 129.1, 129, 118, 117.8, 117.5, 116.2, 116.2, 115.1, 52.5, 31.5, 31.3, 30.7, 27.3, 22.1, 20.6.

[002242] Example 306: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[002243] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a light beige solid.

[002244] 1H NMR (DMSOd6): 8.39 (1 H, br d, J = 6.6 Hz), 7.47 (1 H, dd, J = 6.5, 2.7 Hz), 7 , 43 (1 H, ddd, J = 8.7, 4.3, 2.7 Hz), 7.30 (1 H, dd, J = 9.1, 9.9 Hz), 4.26 (1 H, m), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.80 (1 H, q, J = 7.3 Hz), 3.74 (1 H, dd, J = 9.0, 5.9 Hz), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3, 51 (2 H, m), 3.49 (1 H, dd, J = 3.6, 9.0 Hz), 3.34 (3 H, s), 2.89 (1 H, dd, J = 8.3, 4.2 Hz), 2.10 (1 H, dq, J = 12.7, 7.6 Hz), 1.75 (1 H, m), 1.70 (1 H, dd, J = 8.3, 5.4 Hz), 1.13 (1 H, t, J = 4.8 Hz). 13

[002245] C NMR (DMSOd6): 167.7, 161.3, 159.6, 156.8, 131, 130.2, 130.2, 129.4, 129.3, 128.8, 128, 6, 128.3, 128.3, 117.6, 117.4, 116.1, 72.4, 66.3, 52.4, 52.4, 49.8, 32, 31.5, 31, 4, 31, 22.1, 20.7.

[002246] Example 307: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-

thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) - N - ((R) -tetrahydrofuran-3- il) acetamide

[002247] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo- 2,3,5,5a, 6 , 6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a brown solid.

[002248] 1H NMR (DMSOd6): 11.66 (1 H, s), 8.23 (1 H, br d, J = 6.6 Hz), 7.56 (3 H, m), 7, 24 (2 H, dd, J = 10.1, 8.5 Hz), 4.24 (1 H, m), 4.07 (1 H, d, J = 12.0 Hz), 3.78 ( 2 H, m), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3, 49 (1 H, dd, J = 8.9, 3.7 Hz), 3.30 (2 H, m), 2.81 (1 H, dd, J = 8.4, 4.1 Hz), 2.08 (1 H, m), 1.75 (1 H, m), 1.66 (1 H, dd, J = 8.3, 5.4 Hz), 1.12 (1 H, t, J = 4.8 Hz). 13

[002249] C NMR (DMSOd6): 167.6, 161.8, 160.1, 155.9, 133, 132.3, 132.3, 131.7, 129.3, 129.2, 118, 117.8, 116.2, 113.9, 72.4, 66.3, 51.5, 49.8, 32.2, 32, 31.2, 22.1, 20.7.

[002250] Example 308: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[002251] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002252] 1H NMR (DMSOd6): 8.39 (1 H, d, J = 6.6 Hz), 7.58 (1 H, dd, J = 6.6, 2.5 Hz), 7, 56 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.24 (1 H, dd, J = 10.1, 8.8 Hz), 4.26 (1 H , m), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.2 Hz), 3.80 (1 H, q, J = 7 , 3 Hz), 3.74 (1 H, dd, J = 8.9, 6.0 Hz), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3.51 (2 H, m), 3.49 (1 H, dd, J = 3.7, 9.0 Hz), 3.35 (3 H, s), 2.89 (1 H, dd, J = 8 , 3, 4.2 Hz), 2.09 (1 H, m), 1.75 (1 H, m), 1.70 (1 H, dd, J = 8.3, 5.4 Hz), 1.13 (1 H, t, J = 4.8 Hz).

[002253] 13C NMR (DMSOd6): 167.7, 161.8, 160.1, 156.8, 133, 133, 132.3, 132.3, 131, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 116.1, 72.4, 66.3, 52.4, 49.8, 32, 31.5, 31.4, 31, 22.1, 20, 7.

[002254] Example 309: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -1- (pyrrolidin-1-yl) ethan-1-one

[002255] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002256] 1H NMR (DMSOd6): 7.46 (1 H, dd, J = 6.5, 2.6 Hz), 7.43 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 8.9, 9.8 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H , d, J = 12.0 Hz), 3.72 (2 H, m), 3.52 (2 H, t, J = 6.8 Hz), 3.34 (3 H, s), 3, 32 (2 H, t, J = 7.1 Hz), 2.87 (1 H, dd, J = 8.2, 4.3 Hz), 1.91 (2 H, quin, J = 6.7 Hz), 1.79 (2 H, quin, J = 6.8 Hz), 1.69 (1 H, dd, J = 8.3, 5.4 Hz), 1.12 (1 H, t, J = 4.8 Hz). 13

[002257] C NMR (DMSOd6): 166.2, 161.3, 159.6, 156.8, 130.7, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116, 52.4, 52.4, 46.1, 45.6, 31.6, 31.5, 30.4, 25.6, 24, 22.1, 20.7.

[002258] Example 310: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -1- (pyrrolidin-1-yl) ethan-1-one

[002259] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002260] 1H NMR (DMSOd6): 7.43 (2 H, m), 7.00 (1 H, dd, J = 9.8, 8.6 Hz), 4.23 (1 H, d, J = 12.2 Hz), 3.99 (1 H, d, J = 12.0 Hz), 3.53 (2 H, s), 3.46 (3 H, s), 3.43 (4 H, m), 2.59 (1 H, dd, J = 8.3, 4.2 Hz), 1.98 (2 H, m), 1.87 (2 H, m), 1.61 ( 1 H, dd, J = 8.2, 5.6 Hz), 1.15 (1 H, m). 13

[002261] C NMR (DMSOd6): 166.4, 162.7, 161.1, 158.7, 133.8, 133.8, 133, 132.9, 131.4, 129.4, 129, 3, 118.2, 118.1, 117.1, 117.1, 116, 53.4, 53.4, 47.4, 46.7, 32.4, 32.3, 32.1, 26, 8, 24.9, 22.6, 21.7.

[002262] Example 311: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (piperidin-1-yl) ethan-1-one

[002263] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a off-white solid.

[002264] 1H NMR (DMSOd6): 7.46 (1 H, dd, J = 6.5, 2.7 Hz), 7.43 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 10.1, 8.7 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H , d, J = 12.0 Hz), 3.79 (2 H, m), 3.51-3.40 (4 H, m), 3.32 (3 H, s), 2.87 (1 H, dd, J = 8.4, 4.1 Hz), 1.71 (1 H, dd, J = 8.3, 5.4 Hz), 1.59 (2 H, m), 1.53 (2 H, m), 1.45 (2 H, m), 1.12 (1 H, t, J = 4.8 Hz).

[002265] C NMR (DMSOd6): 166.2, 161.3, 159.6, 156.9, 130.6, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116.3, 52.4, 52.4, 46.2, 42.3, 31.6, 31.5, 29, 1, 26, 25.2, 23.9, 22.1, 20.7.

[002266] Example 312: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (piperidin-1-yl) ethan-1-one

[002267] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a off-white solid.

[002268] 1H NMR (DMSOd6): 7.56 (2 H, m), 7.24 (1 H, dd, J = 10.0, 8.7 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.79 (2 H, m), 3.46 (4 H, m), 3.32 (3 H, s), 2.87 (1 H, dd, J = 8.3, 4.2 Hz), 1.71 (1 H, dd, J = 8.2, 5.4 Hz), 1.59 (2 H, m), 1.53 (2 H, m), 1.45 (2 H, m), 1.11 (1 H, t, J = 4.8 Hz).

[002269] 13C NMR (DMSOd6): 166.2, 161.8, 160.1, 156.9, 133, 133, 132.3, 132.3, 130.6, 129.1, 129, 118, 117.8, 116.3, 116.2, 116.2, 52.4, 52.4, 46.2, 42.3, 31.5, 31.4, 29.1, 26, 25.2, 23.9, 22.1, 20.7.

[002270] Example 313: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002271] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a light beige solid.

[002272] 1H NMR (DMSOd6): 8.14 (1 H, d, J = 7.6 Hz), 7.46 (1 H, dd, J = 6.6, 2.6 Hz), 7, 43 (1 H, ddd, J = 8.7, 4.4, 2.8 Hz), 7.30 (1 H, t, J = 9.3 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.82 (2 H, dt, J = 11.2, 3.1 Hz), 3.78 (1 H, m), 3.50 (2 H, m), 3.35 (2 H, m), 3.35 (3 H, s), 2.88 (1 H, dd, J = 8.4, 4.3 Hz), 1.71 (3 H, m), 1.41 (2 H, m), 1.13 (1 H, t, J = 4.8 Hz). 13

[002273] C NMR (DMSOd6): 166.9, 161.3, 159.6, 156.8, 130.9, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116.2, 65.8, 52.4, 52.4, 45.2, 32.4, 32.4, 31, 5, 31.4, 31.2, 22, 21.6, 20.8.

[002274] Example 314: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002275] The compound was prepared in an analogous way to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002276] 1H NMR (DMSOd6): 8.14 (1 H, d, J = 7.6 Hz), 7.58 (1 H, m), 7.56 (1 H, ddd, J = 6, 5, 4.4, 2.2 Hz), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.2 Hz), 3.82 (2 H, m), 3.77 (1 H, m), 3.50 (2 H, m), 3.35 (3 H, s), 3.34 (2 H, m), 2.88 (1 H, dd, J = 8.4, 4.1 Hz), 1.72 (2 H, m), 1, 71 (1 H, dd, J = 5.4, 8.5 Hz), 1.41 (2 H, m), 1.13 (1 H, t, J = 4.8 Hz). 13

[002277] C NMR (DMSOd6): 166.9, 161.8, 160.1, 156.8, 133.1, 133, 132.3, 132.3, 130.9, 129.2, 129, 1, 118, 117.8, 116.2, 116.2, 65.8, 52.4, 52.4, 45.2, 32.4, 32.3, 31.5, 31.4, 31, 2, 22, 20.7.

[002278] Example 315: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (2,2,2-trifluoroethyl) acetamide

[002279] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (2,3,5,6- tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a light cream powder.

[002280] 1H NMR (DMSOd6): 8.77 (1 H, br t, J = 6.2 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8 , 5 Hz), 4.25 (1 H, dd, J = 11.4, 9.3 Hz), 3.93 (2 H, m), 3.85 (1 H, dd, J = 11.6 , 7.6 Hz), 3.57 (2 H, m), 3.39 (3 H, s), 3.32 (1 H, dd, J = 9.2, 16.0 Hz), 2, 93 (1 H, dd, J = 15.9, 8.0 Hz). 13

[002281] C NMR (DMSOd6): 168.7, 156.5, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144, 6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.6, 127.5, 125.6, 123.8, 121.9, 120.4, 120.3, 120.2, 115.7, 105.9, 105.7, 105.6, 49.4, 39.5, 34.9, 31.4, 30, 9, 29.

[002282] Example 316: (R) -2- (2-methyl-3-thioxo-6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (oxazol-2-yl) acetamide

[002283] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (2,3,5,6- tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002284] 1H NMR (DMSOd6): 11.45 (1 H, br s), 7.87 (1 H, d, J = 0.9

Hz), 7.85 (1 H, m), 7.10 (1 H, d, J = 0.9 Hz), 4.49 (1 H, quin, J = 8.5 Hz), 4.26 (1 H, dd, J = 11.4, 9.3 Hz), 3.86 (1 H, dd, J = 11.7, 7.7 Hz), 3.74 (2 H, m), 3 , 41 (3 H, m), 3.37 (1 H, dd, J = 16.0, 8.4 Hz), 2.96 (1 H, dd, J = 16.0, 7.9 Hz) . 13

[002285] C NMR (DMSOd6): 156.5, 152.9, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144, 6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 136.2, 128.9, 126.6, 120.4, 120.3, 120.2, 115.2, 105.9, 105.7, 105.6, 49.5, 34.8, 31.6, 31.4, 29.1, 29.

[002286] Example 317: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (oxazol-2-yl) acetamide

[002287] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002288] 1H NMR (DMSOd6): 11.44 (1 H, br s), 7.87 (1 H, s), 7.61 (1 H, td, J = 8.7, 5.6 Hz ), 7.21 (1 H, t, J = 9.3 Hz), 7.10 (1 H, s), 4.45 (1 H, quin, J = 8.6 Hz), 4.24 ( 1 H, m), 3.82 (1 H, dd, J = 11.6, 7.8 Hz), 3.78 (2 H, br), 3.41 (3 H, s), 3.31 (1 H, m), 2.92 (1 H, dd, J = 16.0, 8.1 Hz). 13

[002289] C NMR (DMSOd6): 166.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.5, 154.9, 154.9, 152.9, 152.9, 136.2, 129.7, 129.7,

129.1, 126.6, 118.8, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 115.1, 113.2, 113.2, 113.1, 113.1, 49.6, 34.7, 31.6, 31.4, 29.1.

[002290] Example 318: (R) -3- (2-methyl-3-thioxo-6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1- morpholinopropan-1-one

[002291] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -3- (2-methyl-6- (2,3,5,6- tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one and isolated as a yellowish powder.

[002292] 1H NMR (DMSOd6): 7.86 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, br dd, J = 11 , 4, 9.2 Hz), 3.81 (1 H, dd, J = 11.7, 7.8 Hz), 3.52 (4 H, m), 3.45 (3 H, s), 3.41 (4 H, m), 3.38 (1 H, m), 3.01 (1 H, br dd, J = 15.6, 8.0 Hz), 2.72 (2 H, br t, J = 7.3 Hz), 2.62 (2 H, t, J = 7.6 Hz). 13

[002293] C NMR (DMSOd6): 169.5, 155.8, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 143, 7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 126.7, 120.8, 120.5, 120.4, 120.3, 105.9, 105.7, 105.5, 66, 66, 49.1, 45.1, 41.5, 34.9, 31.1, 29.7, 29.2, 19.6.

[002294] Example 319: 1- (6,6-dimethyl-3-azabicyclo [3.1.0] hexan-3-yl) -3- ((R) -2-methyl-6- (2,3,5, 6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one

[002295] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -3- (2-methyl-6- (2,3,5,6- tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one and isolated as a light beige solid.

[002296] 1H NMR (DMSOd6): 7.86 (1 H, m), 4.43 (1 H, m), 4.20 (1 H, m), 3.79 (1 H, m), 3.60 (1 H, m), 3.44 (3 H, s), 3.40-3.29 (3 H, m), 3.26 (1 H, dd, J = 12.4, 7 , 8 Hz), 2.97 (1 H, m), 2.69 (2 H, m), 2.49 (2 H, m), 1.42 (1 H, m), 1.36 (1 H, m), 0.98 (3 H, 2 s), 0.77 (3 H, 2 s). 13

[002297] C NMR (DMSOd6): 168.7, 155.9, 155.8, 146.4, 146.3, 145.3, 145.3, 144.8, 144.7, 143.7, 143.7, 143.6, 126.6, 126.5, 120.8, 120.8, 120.5, 120.4, 120.3, 120.3, 120.2, 120.1, 105, 9, 105.7, 105.6, 49, 49, 45.8, 45.8, 45.5, 34.9, 34.9, 31.3, 31.2, 31.1, 29.3, 29.2, 27.4, 27.3, 25.9, 25.9, 25.9, 19.2, 18.5, 18.5, 12.1, 12.1.

[002298] Example 320: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (piperazin-1-yl) ethan-1-one

[002299] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002300] 1H NMR (DMSOd6): 7.46 (1 H, dd, J = 6.6, 2.6 Hz), 7.43 (1 H, ddd, J = 8.7, 4.4, 2.8 Hz), 7.30 (1 H, dd, J = 8.9, 9.9 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H , d, J = 12.0 Hz), 3.79 (2 H, m), 3.44 (2 H, m), 3.40 (2 H, m), 3.32 (3 H, s) , 2.86 (1 H, dd, J = 8.3, 4.2 Hz), 2.72 (2 H, m), 2.65 (2 H, m), 1.71 (1 H, dd , J = 8.3, 5.4 Hz), 1.12 (1 H, t, J = 4.8 Hz). 13

[002301] C NMR (DMSOd6): 166.5, 161.3, 159.6, 156.9, 130.6, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116.2, 64.9, 62.8, 52.4, 46.5, 45.8, 45.3, 42, 5, 31.6, 31.5, 29, 22.1, 20.7, 15.2.

[002302] Example 321: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -1- (piperazin-1-yl) ethan-1-one hydrochloride

[002303] The compound was prepared in a manner analogous to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one in the reaction with piperazine followed by salt formation in a mixture of ethyl acetate and 2M HCl in diethyl ether. The product was isolated as a yellow solid.

[002304] 1H NMR (DMSOd6): 9.30 (2 H, m), 7.61-7.53 (2 H, m), 7.24 (1 H, dd, J = 9.9, 8 , 7 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.89 (2 H, s), 3.86 (1 H, d, J = 12.2 Hz), 3 , 78 (2 H, m), 3.70 (2 H, m), 3.32 (3 H, s), 3.17 (2 H, m), 3.08 (2 H, m), 2 , 85 (1 H, dd, J = 8.3, 4.2 Hz), 1.71 (1 H, dd, J = 8.3, 5.4 Hz), 1.13 (1 H, t, J = 4.8 Hz).

[002305] 13C NMR (DMSOd6): 167, 161.8, 160.1, 157, 133.1, 133.1, 132.4, 132.3, 130.9, 129.1, 129, 118, 117.9, 116.2, 116.2, 115.7, 52.4, 42.6, 42.4, 42.1, 38.1, 31.6, 31.5, 28.8, 22, 1, 20.7.

[002306] Example 322: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -1- (2- (cyclopentylamino) ethyl) -2-methyl-5,5a, 6,6a-tetrahydrochloride - hydrocycloprop [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[002307] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N-cyclopentylacetamide (Example 273) and isolated as a yellow solid.

[002308] 1H NMR (DMSOd6): 8.71 (1 H, br s), 8.64 (1 H, br s), 7.49 (1 H, dd, J = 6.4, 2.6 Hz), 7.45 (1 H, m), 7.31 (1 H, t, J = 9.3 Hz), 4.15 (1

H, d, J = 12.2 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.55 (1 H, m), 3.44 (3 H, s), 3 , 18 (2 H, br s), 3.03 (1 H, dd, J = 8.4, 4.3 Hz), 2.97 (2 H, m), 1.99 (2 H, m) , 1.71 (3 H, m), 1.62 (2 H, td, J = 12.8, 6.4 Hz), 1.56 (2 H, m), 1.21 (1 H, t , J = 4.8 Hz). 13

[002309] C NMR (DMSOd6): 161.3, 159.6, 157.3, 130.9, 130.2, 130.2, 129.4, 129.4, 128.7, 128.6, 128.3, 128.3, 117.6, 117.5, 116.3, 58.2, 52.4, 43.8, 31.7, 31.3, 29.2, 29.1, 23, 6, 22, 21, 20.6.

[002310] Example 323: (R) -4- (2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) piperazin-2-one

[002311] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (2,3,5,6- tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a beige powder.

[002312] 1H NMR (DMSOd6): 8.17, 8.11 (1 H, 2 s), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz ), 4.25 (1 H, dd, J = 9.7, 11.1 Hz), 4.11 (1 H, s), 3.94 (1 H, s), 3.84 (1 H, dd, J = 11.7, 7.7 Hz), 3.79 (2 H, m), 3.66 (1 H, m), 3.61 (1 H, m), 3.36 (3 H , 2 s), 3.32-3.25 (2 H, m), 3.17 (1 H, m), 2.90 (1 H, br dd, J = 15.8, 7.8 Hz) . 13

[002313] C NMR (DMSOd6): 166.9, 166.7, 166.4, 165.8, 156.3, 156.3, 146.4, 146.4, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.3,

145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143, 6, 128.2, 128.1, 120.5, 120.4, 120.4, 120.3, 120.3, 120.2, 116.1, 116, 105.9, 105.7, 105, 5, 49.4, 48.2, 45.7, 42.1, 38.4, 34.9, 34.9, 31.5, 29, 29.

[002314] Example 324: (R) -1-methyl-4- (2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) piperazin-2-one

[002315] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (2,3,5,6- tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002316] 1H NMR (DMSOd6): 7.86 (1 H, m), 4.48 (1 H, quin, J = 8.1 Hz), 4.25 (1 H, br t, J = 10 , 3 Hz), 4.16 (1 H, s), 4.00 (1 H, s), 3.90-3.73 (4 H, m), 3.69 (1 H, m), 3 , 41 (1 H, m), 3.39-3.34 (3 H, m), 3.32-3.25 (2 H, m), 2.90 (1 H, m), 2.86 (3 H, s). 13

[002317] C NMR (DMSOd6): 166.6, 166.5, 164.6, 164, 156.3, 156.3, 146.4, 146.4, 146.3, 146.2, 146, 2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.1, 120.5, 120, 4, 120.3, 116.1, 116, 105.9, 105.7, 105.5, 49.4, 48.4, 47.5, 47, 45.8, 42.1, 38.3, 34.9, 33.7, 33.5, 31.5, 29, 29, 28.8.

[002318] Example 325: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-

methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N - ((1r, 4R) - 4-hydroxycyclohexyl) acetamide

[002319] The compound was prepared analogously to Example 25 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one using DIPEA as base and isolated as a beige solid.

[002320] 1H NMR (DMSOd6): 7.98 (1 H, d, J = 7.8 Hz), 7.90-7.53 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.54 (1 H, d, J = 4.4 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.84 ( 1 H, d, J = 12.0 Hz), 3.47 (3 H, m), 3.37 (1 H, m), 3.34 (3 H, s), 2.87 (1 H, dd, J = 8.4, 4.3 Hz), 1.79 (4 H, m), 1.69 (1 H, dd, J = 8.4, 5.4 Hz), 1.19 (4 H, m), 1.12 (1 H, t, J = 4.8 Hz). 13

[002321] C NMR (DMSOd6): 166.8, 161.8, 160.1, 156.8, 133.1, 133, 132.3, 132.3, 130.9, 129.2, 129, 1, 118, 117.8, 116.3, 116.2, 116.2, 68.1, 62.8, 52.4, 47.5, 33.9, 31.5, 31.4, 31, 3, 30.2, 30.1, 22, 20.7.

[002322] Example 326: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (4-methylpiperazin-1-yl) ethan-1-one

[002323] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002324] 1H NMR (DMSOd6): 7.46 (1 H, dd, J = 6.5, 2.7 Hz), 7.44 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 9.9, 8.9 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H , d, J = 12.0 Hz), 3.82 (2 H, m), 3.58 (4 H, m), 3.32 (3 H, s), 2.85 (1 H, dd, J = 8.3, 4.2 Hz), 2.65-2.36 (4H, m br), 2.30 (3 H, br s), 1.71 (1 H, dd, J = 8, 3, 5.4 Hz), 1.12 (1 H, t, J = 4.8 Hz). 13

[002325] C NMR (DMSOd6): 166.6, 161.3, 159.6, 156.9, 130.7, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116, 54.3, 53.9, 52.4, 45.1, 44.6, 40.8, 31.6, 31.5, 29, 22.1, 20.7.

[002326] Example 327: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[002327] The compound was prepared in an analogous manner to Example 34 from (S) -2- (2-methyl-3-thioxo-6- (3-chloro-2,6-difluorophenyl) - 2.5 acid, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white solid.

[002328] 1H NMR (DMSOd6): 8.11 (1 H, br d, J = 7.3 Hz), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7 , 22 (1 H, t, J = 9.4 Hz), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.3, 9, 4 Hz), 3.80 (1 H, dd, J = 11.5, 7.8 Hz), 3.65 (3 H, m), 3.44 (2 H, m), 3.39 (3 H, s), 3.33 (1H, m), 3.29 (1 H, m), 3.11 (1 H, m), 2.88 (1 H, dd, J = 15.8, 8 , 1 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.46 (2 H, m). 13

[002329] C NMR (DMSOd6): 167.3, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.7, 118.6, 116.4, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 70.1, 67, 49.5, 45.1, 34.7, 31.5, 31.2, 29.2, 28.5, 23.8

[002330] Example 328: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (pyrazin-2-ylmethyl) acetamide

[002331] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002332] 1H NMR (DMSOd6): 8.74 (1 H, br t, J = 5.7 Hz), 8.59 (1 H, s), 8.55 (1 H, dd, J = 2 , 4, 1.5 Hz), 8.51 (1 H, d, J = 2.5 Hz), 7.62 (1 H, td,

J = 8.7, 5.6 Hz), 7.22 (1 H, t, J = 9.4 Hz), 4.43 (3 H, m), 4.22 (1 H, m), 3 , 80 (1 H, dd, J = 11.5, 8.0 Hz), 3.56 (2 H, d, J = 5.9 Hz), 3.40 (3 H, m), 3.25 (1 H, dd, J = 15.8, 9.3 Hz), 2.85 (1 H, dd, J = 15.8, 8.3 Hz). 13

[002333] C NMR (DMSOd6): 168.2, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 153.9, 143.9, 143.5, 143.2, 129.7, 129.7, 128.6, 118.6, 118.5, 118.4, 116.1, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 49.4, 42.4, 34.7, 31.4, 31.2, 29.1.

[002334] Example 329: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1-morpholinoetan-1-one

[002335] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002336] 1H NMR (DMSOd6): 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, t, J = 9.4 Hz), 4, 44 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, m), 3.80 (1 H, dd, J = 11.5, 7.7 Hz), 3.75 ( 2 H, s), 3.59 (2 H, m), 3.55 (2 H, m), 3.49 (2 H, m), 3.45 (2 H, m), 3.36 ( 3 H, m), 3.27 (1 H, dd, J = 15.9, 9.3 Hz), 2.86 (1 H, dd, J = 15.9, 7.8 Hz). 13

[002337] C NMR (DMSOd6): 166.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.2, 118.9, 118.8, 118.6, 116.2, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 66, 66, 49.5, 45.6, 41.7, 34.8, 31.5, 29.2, 28.8.

[002338] Example 330: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (cyclopentylamino) ethyl) -2-methyl-5,5a, 6,6a-tetrahydrochloride - hydrocycloprop [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[002339] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N-cyclopentylacetamide (Example 272) and isolated as a beige solid.

[002340] 1H NMR (DMSOd6): 8.77 (2 H, m), 7.61 (1 H, dd, J = 6.7, 2.6 Hz), 7.57 (1 H, ddd, J = 8.7, 4.5, 2.5 Hz), 7.25 (1 H, dd, J = 10.1, 8.8 Hz), 4.14 (1 H, d, J = 11, 9 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.54 (1 H, m), 3.43 (3 H, s), 3.17 (2 H, br s ), 3.04 (1 H, dd, J = 8.4, 4.3 Hz), 2.98 (2 H, m), 1.99 (2 H, m), 1.71 (3 H, m), 1.63 (2 H, m), 1.55 (2 H, m), 1.20 (1 H, t, J = 4.8 Hz). 13

[002341] C NMR (DMSOd6): 161.8, 160.2, 157.2, 133.1, 133, 132.4, 132.4, 130.9, 129.2, 129.1, 118, 117.9, 116.3, 116.2, 58.2, 52.4, 43.8, 31.7, 31.3, 29.2, 29.1, 23.7, 22, 21, 20, 6.

[002342] Example 331: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-1- (2 - (((R) -tetrahydro-2H-pyran-3-hydrochloride -yl) amino) ethyl) - 5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[002343] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- ((R) -tetrahydro-2H-pyran-3-yl) acetamide (Example 277) and isolated as a beige solid.

[002344] 1H NMR (DMSOd6): 9.05 (2 H, m), 7.61 (1 H, dd, J = 6.7, 2.6 Hz), 7.57 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.25 (1 H, dd, J = 10.1, 8.8 Hz), 4.14 (1 H, d, J = 12, 0 Hz), 3.90 (1 H, dd, J = 11.6, 2.6 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.66 (1 H, m ), 3.59 (1 H, dd, J = 11.7, 7.1 Hz), 3.49 (1 H, ddd, J = 11.2, 8.2, 2.9 Hz), 3, 43 (3 H, s), 3.22 (3 H, m), 3.03 (3 H, m), 2.07 (1 H, td, J = 8.9, 4.4 Hz), 1 , 77 (2 H, m), 1.69 (1 H, dd, J = 8.3, 5.4 Hz), 1.52 (1 H, m), 1.19 (1 H, t, J = 4.8 Hz).

[002345] 13C NMR (DMSOd6): 161.8, 160.2, 157.2, 133, 133, 132.4, 132.4, 130.7, 129.2, 129.1, 118, 117, 9, 116.4, 116.2, 116.2, 67.3, 66.7, 52.4, 52.4, 42.4, 31.7, 31.4, 24.7, 22.4, 22.1, 20.9, 20.6.

[002346] Example 332: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa hydrochloride - hydrocycloprop [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- (pyridin-2-ylmethyl) acetamide

[002347] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a light green solid.

[002348] 1H NMR (DMSOd6): 8.99 (1 H, br t, J = 5.6 Hz), 8.74 (1 H, br d, J = 5.3 Hz), 8.32 ( 1 H, br t, J = 7.5 Hz), 7.75 (2 H, m), 7.47 (1 H, dd, J = 6.5, 2.6 Hz), 7.44 (1 H, ddd, J = 8.7, 4.3, 2.7 Hz), 7.31 (1 H, dd, J = 9.8, 8.9 Hz), 4.61 (2 H, br d , J = 5.6 Hz), 4.15 (1 H, br d, J = 11.9 Hz), 3.86 (1 H, br d, J = 12.0 Hz), 3.71 (2 H, br m), 3.36 (3 H, s), 2.94 (1 H, dd, J = 8.3, 4.2 Hz), 1.68 (1 H, dd, J = 8, 4, 5.4 Hz), 1.16 (1 H, m). 13

[002349] C NMR (DMSOd6): 168.8, 161.2, 159.6, 156.8, 155.5, 143.7, 143.3, 131.4, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 124.4, 124, 117.6, 117.4, 115.7, 52.5, 41.7, 31.6, 31.5, 30.9, 22.1, 20.7.

[002350] Example 333: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[002351] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002352] 1H NMR (DMSOd6): 8.84 (1 H, d, J = 6.6 Hz), 7.62 (1 H, td, J = 8.7, 5.6 Hz), 7, 22 (1 H, t, J = 9.4 Hz), 4.78 (1 H, m), 4.70 (2 H, m), 4.42 (3 H, m), 4.22 (1 H, dd, J = 11.4, 9.3 Hz), 3.80 (1 H, dd, J = 11.7, 7.7 Hz), 3.47 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.4 Hz), 2.90 (1 H, dd, J = 15.8, 8.1 Hz). 13

[002353] C NMR (DMSOd6): 167.4, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 129.7, 129.6, 128.6, 118.7, 118.6, 118.5, 116.1, 116, 116, 115.9, 115.9, 113.2, 113.2, 113, 1, 113.1, 77, 76.9, 49.5, 44.2, 34.7, 31.5, 31, 29.1.

[002354] Example 334: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-1- (2 - (((2,2,2-trifluoroethyl) amino) ethyl) hydrochloride) - 5.5a, 6.6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[002355] The compound was prepared in an analogous manner to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- (2,2,2-trifluoroethyl) acetamide (Example 298) and isolated as a beige solid.

[002356] 1H NMR (DMSOd6): 10.19 (2 H, m), 7.61 (1 H, dd, J = 6.7, 2.6 Hz), 7.57 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.25 (1 H, dd, J = 10.1, 8.8 Hz), 4.14 (1 H, br d, J = 11 , 9 Hz), 4.09 (2 H, m), 3.84 (1 H, d, J = 12.0 Hz), 3.42 (3H, s), 3.27 (2 H, br d , J = 7.5 Hz), 3.08 (2 H, m), 2.99 (1 H, dd, J = 8.3, 4.2 Hz), 1.69 (1 H, dd, J = 8.4, 5.4 Hz), 1.20 (1 H, t, J = 4.8 Hz).

[002357] 13C NMR (DMSOd6): 161.8, 160.1, 157.2, 133, 133, 132.4, 132.4, 130.8, 129.1, 129, 126.1, 124, 3, 122.4, 120.6, 118, 117.8, 116.4, 116.2, 116.2, 52.4, 46.7, 46.5, 46.2, 46, 45.9, 31.6, 31.3, 22, 20.8, 20.6.

[002358] Example 335: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa hydrochloride - hydrocycloprop [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- (pyrazin-2-ylmethyl) acetamide

[002359] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a orange solid.

[002360] 1H NMR (DMSOd6): 8.79 (1 H, t, J = 5.7 Hz), 8.61 (1 H, d, J = 1.3 Hz), 8.58 (1 H , dd, J = 2.4, 1.5 Hz), 8.53 (1 H, d, J = 2.6 Hz), 7.46 (1 H, dd, J = 6.5, 2.7 Hz), 7.44 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 9.8, 8.9 Hz), 4 , 46 (2 H, m), 4.16 (1 H, br d, J = 12.2 Hz), 3.87 (1 H, d, J = 12.0 Hz), 3.66 (2 H , m), 3.37 (3 H, s), 2.92 (1 H, dd, J = 8.4, 4.3 Hz), 1.67 (1 H, dd, J = 8.3, 5.4 Hz), 1.17 (1 H, m). 13

[002361] C NMR (DMSOd6): 168.2, 161.2, 159.6, 153.9, 144, 143.9, 143.4, 143.2, 131.8, 130.2, 130, 2, 129.4, 129.4, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116.2, 52.5, 42.4, 31.6, 31.5, 31, 22.1, 20.7.

[002362] Example 336: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((((S) -tetrahydrofuran-2-yl) methyl) acetamide

[002363] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002364] 1H NMR (DMSOd6): 8.18 (1 H, br t, J = 5.6 Hz), 7.62 (1 H, td, J = 8.7, 5.6 Hz), 7 , 22 (1 H, t, J = 9.4 Hz), 4.43 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, m), 3.81 (2 H, m), 3.72 (1 H, m), 3.58 (1 H, m), 3.45 (2 H, m), 3.40 (3 H, s), 3.28 (1 H, dd, J = 15.8, 9.3 Hz), 3.17 (1 H, m), 3.08 (1 H, m), 2.89 (1 H, dd, J = 15.8, 8 , 1 Hz), 1.85 (1 H, m), 1.78 (2 H, m), 1.46 (1 H, m). 13

[002365] C NMR (DMSOd6): 167.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.6, 118.5, 116.4, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 77, 67.1, 49.4, 42.9, 34.7, 31.4, 31.2, 29.1, 28.4, 25.1.

[002366] Example 337: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((((R) -tetrahydrofuran-2-yl) methyl) acetamide

[002367] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002368] 1H NMR (DMSOd6): 8.18 (1 H, br t, J = 5.6 Hz), 7.62 (1 H, td, J = 8.7, 5.6 Hz), 7 , 21 (1 H, m), 4.43 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, m), 3.81 (2 H, m), 3.72 ( 1 H, m), 3.58 (1 H, m), 3.45 (2 H, m), 3.40 (3

H, s), 3.28 (1 H, dd, J = 15.8, 9.4 Hz), 3.16 (1 H, m), 3.10 (1 H, m), 2.89 ( 1 H, dd, J = 15.8, 8.1 Hz), 1.85 (1 H, m), 1.78 (2 H, m), 1.46 (1 H, m). 13

[002369] C NMR (DMSOd6): 167.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.6, 118.5, 116.4, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 77, 67.1, 49.5, 42.9, 34.7, 31.4, 31.2, 29.1, 28.4, 25.1.

[002370] Example 338: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - (((1-methyl-1H-pyrazol-4-yl) methyl) acetamide

[002371] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002372] 1H NMR (DMSOd6): 8.36 (1 H, t, J = 5.5 Hz), 7.62 (1 H, td, J = 8.7, 5.6 Hz), 7, 54 (1 H, s), 7.29 (1 H, s), 7.22 (1 H, m), 4.42 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, m), 4.08 (2 H, m), 3.80 (1 H, dd, J = 11.5, 8.0 Hz), 3.75 (3 H, s), 3.44 ( 2 H, m), 3.38 (3 H, s), 3.23 (1 H, dd, J = 15.8, 9.3 Hz), 2.85 (1 H, dd, J = 15, 8, 8.3 Hz). 13

[002373] C NMR (DMSOd6): 167.3, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 137.9, 129.7, 129.7, 129.4, 128.4, 118.7, 118.5, 118.4, 116.4, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 49.4, 38.3, 34.7, 33.2, 31.4, 31.2, 29.1.

[002374] Example 339: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrole [1,2-

c] imidazol-1-yl) -N - (((1-methyl-1H-pyrazol-4-yl) methyl) acetamide

[002375] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002376] 1H NMR (DMSOd6): 8.39 (1 H, br t, J = 5.5 Hz), 7.56 (1 H, s), 7.46 (1 H, dd, J = 6 , 5, 2.6 Hz), 7.43 (1 H, ddd, J = 8.6, 4.3, 2.8 Hz), 7.31 (2 H, m), 4.12 (3 H , m), 3.85 (1 H, d, J = 12.0 Hz), 3.77 (3 H, s), 3.52 (2 H, m), 3.33 (3 H, m) , 2.87 (1 H, dd, J = 8.4, 4.1 Hz), 1.67 (1 H, dd, J = 8.3, 5.4 Hz), 1.15 (1 H, t, J = 4.8 Hz). 13

[002377] C NMR (DMSOd6): 167.5, 161.3, 159.6, 156.9, 137.9, 131.1, 130.2, 130.2, 129.4, 129.4, 129.3, 128.8, 128.7, 128.3, 128.3, 118.5, 117.6, 117.4, 116, 52.4, 38.4, 33.2, 31.5, 31.4, 31.1, 22, 20.7.

[002378] Example 340: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (thiazol-2-yl) acetamide

[002379] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (2,3,5,6- tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002380] 1H NMR (DMSOd6): 12.39 (1 H, s), 7.85 (1 H, m), 7.48 (1 H, d, J = 3.5 Hz), 7.23 (1 H, d, J = 3.5 Hz), 4.50 (1 H, quin, J = 8.5 Hz), 4.26 (1 H, dd, J = 11.4, 9.3 Hz ), 3.86 (1 H, dd, J = 7.7, 11.4 Hz), 3.84 (2 H, m), 3.43 (3 H, s), 3.36 (1 H, m), 2.96 (1 H, dd, J = 16.0, 7.9 Hz). 13

[002381] C NMR (DMSOd6): 167, 157.8, 156.6, 146.4, 146.4, 146.3, 146.3, 146.2, 145.4, 145.3, 145, 3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 137.7, 129, 120.4, 120.3, 120.2, 115.1, 113.8, 105.9, 105.7, 105.6, 49.5, 34.8, 31.6, 30.8, 29.1.

[002382] Example 341: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -1- (2- (cyclohexylamino) ethyl) -2-methyl-5.5a, 6.6a hydrochloride -tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[002383] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N-cyclohexylacetamide (Example 294) and isolated as a beige solid.

[002384] 1H NMR (DMSOd6): 8.69 (2 H, m), 7.61 (1 H, dd, J = 6.7, 2.6 Hz), 7.57 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.25 (1 H, dd, J = 10.1, 8.7 Hz), 4.14 (1 H, d, J = 12, 0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.43 (3 H, s), 3.20 (2 H, m), 3.01 (4 H, m) , 2.06 (2 H, m), 1.77 (2 H, m), 1.70 (1 H, dd, J = 8.2, 5.3 Hz), 1.61 (1 H, m ), 1.27 (4 H, m), 1.19 (1 H, t, J = 4.8 Hz), 1.12 (1 H, m). 13

[002385] C NMR (DMSOd6): 161.8, 160.2, 157.2, 133.1, 132.4, 132.4, 130.8, 129.1, 129, 118, 117.9, 116.4, 116.2, 116.2, 55.8, 52.4, 41.6, 31.7, 31.3, 28.7, 28.5, 24.7, 23.9, 23, 9, 22, 21, 20.6.

[002386] Example 342: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -2-oxopyrrolidin-3-yl) acetamide

[002387] The compound was prepared analogously to Example 22 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002388] 1H NMR (DMSOd6): 8.37 (1 H, d, J = 8.1 Hz), 7.84 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, t, J = 9.2 Hz), 4.43 (1 H, quin, J = 8.4 Hz), 4.28 (1 H, m), 4.22 (1 H, br t , J = 10.3 Hz), 3.80 (1 H, dd, J = 11.4, 8.1 Hz), 3.47 (2 H, s), 3.42 (3 H, s), 3.16 (2 H, m), 2.89 (1 H, br dd, J = 15.8, 8.3 Hz), 2.29 (1 H, m), 1.81 (1 H, m ). 13

[002389] C NMR (DMSOd6): 174.2, 167.8, 160.9, 160.8, 159.2, 159.2, 157.6, 157.5, 156.2, 156, 155, 9, 132.5, 132.5, 128.6, 118.6, 118.5, 118.4, 116.2, 113.8, 113.8, 113.7, 113.6, 104.1, 104.1, 103.9, 103.9, 49.9, 49.5, 38, 34.8, 31.4, 31.3, 29.1, 28.2.

[002390] Example 343: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-1- (2 - (((pyridin-2-ylmethyl) amino) ethyl) -5, chlorirdate), 5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[002391] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3 hydrochloride , 5.5a, 6.6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- (pyridin-2-ylmethyl) acetamide (Example 332) and isolated as a light yellow solid.

[002392] 1H NMR (DMSOd6): 9.45 (2 H, br s), 8.66 (1 H, br d, J = 4.7 Hz), 7.92 (1 H, td, J = 7.7, 1.5 Hz), 7.57 (1 H, d, J = 7.8 Hz), 7.47 (3 H, m), 7.32 (1 H, t, J = 9, 3 Hz), 4.39 (2 H, br s), 4.15 (1 H, br d, J = 11.9 Hz), 3.86 (1 H, m), 3.43 (3 H, s), 3.29 (2 H, m), 3.07 (3 H, m), 1.69 (1 H, dd, J = 8.1, 5.4 Hz), 1.21 (1 H , br t, J = 4.6 Hz). 13

[002393] C NMR (DMSOd6): 161.3, 159.6, 157.4, 151.9, 148.9, 137.6, 131.1, 130.2, 130.2, 129.5, 129.4, 128.7, 128.6, 128.3, 128.3, 123.8, 123.3, 117.6, 117.4, 116.3, 52.4, 50.1, 44, 9, 31.7, 31.4, 22.1, 20.8, 20.6.

[002394] Example 344: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -1 - ((R) -2- (trifluoromethyl) pyrrolidin-1-yl) ethan-1-one

[002395] The compound was prepared in an analogous manner to Example 25 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002396] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.18 (1 H, m), 5.04 (0.2 H, quin, J = 7.8 Hz), 4 , 76 (0.8 H, quin, J = 8.2 Hz), 4.45 (1 H, m), 4.24 (1 H, dd, J = 9.5, 11.3 Hz), 3 , 82 (1 H, dd, J = 7.7, 11.5 Hz), 3.79 (2 H, m), 3.64 (2 H, m), 3.35 (3 H, m), 3.30 (1 H, dd, J = 15.8, 9.7 Hz), 2.89 (1 H, br dd, J = 15.8, 8.1 Hz), 2.15-1.84 (4 H, m). 13

[002397] C NMR (DMSOd6): 168.6, 168.1, 156.9, 156.9, 156.9, 156.4, 156.3, 155.3, 155.3, 155.3, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 145.9, 145.9, 145.9, 145.8, 128.6, 127, 125.1, 119, 118.9, 118.9, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116, 115.8, 112, 112, 112, 111.9, 111, 8, 111.8, 111.8, 111.8, 57.5, 57.3, 56.7, 56.5, 56.3, 56.1, 49.5, 46.9, 34.7, 31.5, 31.4, 30.5, 29.5, 29.2, 29.1, 26.2, 24.8, 23.6, 21.3.

[002398] Example 345: N- (2-cyanocyclopentyl) -2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002399] The compound was prepared in an analogous manner to Example 25 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002400] 1H NMR (DMSOd6): 8.55 (0.5 H, d, J = 7.6 Hz), 8.39 (0.5 H, dd, J = 7.6, 2.4 Hz ), 7.47 (1 H, m), 7.18 (1 H, m), 4.43 (1 H, m), 4.24 (2 H, m), 3.82 (1 H, m ), 3.52 (1 H, m), 3.47 (1 H, s), 3.42, 3.40 (3 H, 2 s), 3.32 - 3.23 (1.5 H, m), 2.93 (1 H, m), 2.83 (0.5 H, m), 2.15-2.0 (1 H, m), 1.99-1.88 (1 H, m), 1.89-1.74 (1.5 H, m), 1.74-1.64 (1 H, m), 1.62-1.52 (1 H, m), 1.47 (0.5 H, m). 13

[002401] C NMR (DMSOd6): 167.8, 167.7, 157, 156.9, 156.3, 156.2, 156.2, 155.4, 155.3, 155.3, 149, 1, 149.1, 149, 147.6, 147.5, 147.5, 147.3, 145.9, 145.9, 145.9, 145.8, 128.5, 122, 120.7, 120.7, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 116.3, 116.3, 116.1, 116, 1, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 54.4, 54.4, 51.4, 49.4, 34.7, 33, 9, 33.9, 33.7, 33.7, 31.5, 31.4, 31.3, 31.2, 30.9, 30.9, 30.1, 29.1, 29.1, 28.8, 28.6, 28.6, 22.3, 22.3, 22.1.

[002402] Example 346: (5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-1- (2 - ((((1-methyl-1H-pyrazol-4-yl) hydrochloride) methyl) amino) ethyl) - 5,5a, 6,6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[002403] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N - ((1-methyl-1H-pyrazol-4-yl) methyl) acetamide ( Example 339) and isolated as a beige solid.

[002404] 1H NMR (DMSOd6): 9.25 (2 H, m), 7.84 (1 H, s), 7.58 (1 H, s), 7.50 (1 H, dd, J = 6.5, 2.6 Hz), 7.44 (1 H, m), 7.31 (1 H, t, J = 9.4 Hz), 4.14 (1 H, br d, J = 12.0 Hz), 4.05 (2 H, br t, J = 5.5 Hz), 3.84 (4 H, m), 3.42 (3 H, s), 3.15 (2 H , m), 3.03 (3 H, m), 1.67 (1 H, dd, J = 8.2, 5.4 Hz), 1.20 (1 H, t, J = 4.7 Hz ). 13

[002405] C NMR (DMSOd6): 159.6, 157.2, 139.7, 131.8, 130.9, 130.2, 130.2, 129.4, 129.4, 128.7, 128.6, 128.3, 117.6, 117.4, 116.5, 111.2, 52.4, 43.9, 40.5, 38.6, 31.7, 31.4, 22, 8, 22.1, 20.7.

[002406] Example 347: (R) -N- (isoxazol-4-yl) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002407] The compound was prepared in a manner analogous to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002408] 1H NMR (DMSOd6): 10.49 (1 H, s), 9.11 (1 H, s), 8.63 (1 H, s), 7.47 (1 H, m), 7.18 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.25 (1 H, dd, J = 9.6, 11.2 Hz), 3, 83 (1 H, dd, J = 11.4, 8.1 Hz), 3.71 (2 H, m), 3.43 (3H, s), 3.32 (1 H, dd, J = 9 , 3, 16.1 Hz), 2.94 (1 H, dd, J = 15.9, 8.3 Hz).

[002409] 13C NMR (DMSOd6): 166.3, 159.2, 157, 157, 156.9, 156.9, 156.5, 155.3, 155.3, 149.1, 149, 149, 149, 147.5, 147.5, 147.5, 147.4, 147.4, 147.2, 145.9, 145.9, 145.9, 145.8, 144.3, 144.3, 128.9, 119.6, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 115.5, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 49.5, 34.7, 31.6, 31.1, 29.1.

[002410] Example 348: (S) -1- (2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra- hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) pyrrolidine-3-carbonitrile

[002411] The compound was prepared in an analogous manner to Example 25 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002412] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.18 (1 H, t, J = 9.6 Hz), 4.45 (1 H, quin, J = 8, 6 Hz), 4.24 (1 H, dd, J = 9.5, 11.3 Hz), 3.88-3.40 (8 H, several mult.), 3.37 (3 H, s) , 3.29 (1 H, dd, J = 9.2, 15.8 Hz), 2.90 (1

H, m), 2.32 (0.5 H, m), 2.21 (1 H, m), 2.10 (0.5 H, m). 13

[002413] C NMR (DMSOd6): 166.6, 166.4, 156.9, 156.9, 156.9, 156.9, 156.3, 155.3, 155.3, 149.1, 149, 149, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 145, 8, 128.4, 121.1, 120.9, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 115.9, 115.9, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 49.5, 48.7, 48.6, 44.8, 44.6, 34.7, 31.5, 30.2, 30.1, 29.6, 29.1, 28.1, 28, 26.5.

[002414] Example 349: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (5-methyl-1,3,4-oxadiazol-2-yl) acetamide

[002415] The compound was prepared in an analogous manner to Example 168 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5-acid, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white solid.

[002416] 1H NMR (DMSOd6): 11.78 (1 H, m), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m) , 4.45 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 11.3, 9.4 Hz), 3.82 (3 H, br dd, J = 11.4, 7.7 Hz), 3.41 (3 H, m), 3.33 (1 H, m), 2.93 (1 H, dd, J = 15.9, 8.0 Hz ), 2.43 (3 H, s). 13

[002417] C NMR (DMSOd6): 166.8, 160.5, 160.1, 160.1, 158.5, 158.4, 157, 156.6, 156.5, 154.9, 154, 9, 129.7, 129.7, 129.3, 118.8, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 114.8, 113.2, 113, 2, 113.1, 113.1, 49.6, 34.7, 31.6, 31.5, 29.2, 10.6.

[002418] Example 350: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-

thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (1-methyl-1H-pyrazol-4-yl) acetamide

[002419] The compound was prepared analogously to Example 168 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white solid.

[002420] 1H NMR (DMSOd6): 10.16 (1 H, s), 7.85 (1 H, s), 7.61 (1 H, td, J = 8.7, 5.6 Hz) , 7.39 (1 H, s), 7.21 (1 H, t, J = 9.4 Hz), 4.45 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, m), 3.81 (1 H, br dd, J = 11.4, 7.9 Hz), 3.77 (3 H, s), 3.62 (2 H, m), 3.42 (3H, s), 3.29 (1 H, m), 2.90 (1 H, br dd, J = 15.8, 8.1 Hz). 13

[002421] C NMR (DMSOd6): 165, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 129, 7, 129.7, 129.6, 128.7, 128.6, 121.4, 121.2, 118.7, 118.6, 118.5, 116.1, 113.3, 113.2, 113.1, 113.1, 49.5, 38.6, 34.7, 31.5, 31.3, 29.1.

[002422] Example 351: (R) -N- (isothiazol-4-yl) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002423] The compound was prepared in an analogous way to Example 168 from (S) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002424] 1H NMR (DMSOd6): 10.87 (1 H, s), 8.88 (1 H, s), 8.59 (1 H, s), 7.47 (1 H, m), 7.18 (1 H, m), 4.45 (1 H, quin, J = 8.7 Hz), 4.25 (1 H, dd, J = 9.5, 11.4 Hz), 3, 83 (1 H, dd, J = 11.5, 8.0 Hz), 3.72 (2 H, m), 3.44 (3 H, s), 3.33 (1 H, dd, J = 9.5, 15.8 Hz), 2.94 (1 H, dd, J = 15.8, 8.4 Hz).

[002425] 13C NMR (DMSOd6): 166.2, 157, 157, 156.9, 156.5, 155.3, 155.3, 155.3, 150.8, 149.1, 149, 149, 149, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 145.8, 134.7, 132.6, 128.8, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 115.7, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 49.5, 34.7, 31.6, 31.4, 29.1.

[002426] Example 352: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((tetrahydro-2H-pyran-4-yl) methyl) acetamide

[002427] The compound was prepared in an analogous manner to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002428] 1H NMR (DMSOd6): 8.09 (1 H, br t, J = 5.7 Hz), 7.62 (1 H, td, J = 8.8, 5.6 Hz), 7 , 22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, m), 3.81 (3 H, m), 3.44 ( 2 H, m), 3.40 (3 H, s), 3.29 (1 H, m), 3.22 (2 H, tt, J = 11.7, 2.3 Hz), 2.96 (2 H, m), 2.88 (1 H, dd, J = 15.8, 8.1 Hz), 1.62 (1 H, m), 1.51 (2 H, br d, J = 12.6 Hz), 1.13 (2 H, m). 13

[002429] C NMR (DMSOd6): 167.8, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.7, 128.4, 118.8, 118.7, 118.5, 116.5, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 66.7, 49.5, 44.5, 34.7, 34.7, 31.5, 31.2, 30.3, 29.2.

[002430] Example 353: 1- (3- (fluoromethyl) pyrrolidin-1-yl) -2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2, 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one

[002431] The compound was prepared in an analogous manner to Example 32 from (S) -2- (6- (2,3,6-trifluorophenyl) -2-methyl-3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002432] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.18 (1 H, m), 4.54-4.34 (3 H, m), 4.24 (1 H , dd, J = 9.6, 11.0 Hz), 3.81 (1 H, dd, J = 11.6, 7.9 Hz), 3.75-3.58 (3 H, m), 3.55-3.44 (1.5 H, m), 3.37 (3 H, m), 3.29 (2 H, m), 3.12 (0.5 H, m), 2, 88 (1 H, m), 2.67 (0.5 H, m), 2.53 (0.5 H, m), 2.05 (0.5 H, m), 1.94 (0, 5 H, m), 1.77 (0.5 H, m), 1.64 (0.5 H, m). 13

[002433] C NMR (DMSOd6): 166.3, 166.2, 157, 156.9, 156.9, 156.9, 156.2, 155.3, 155.3, 155.3, 155, 3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.3, 128.2, 128.2, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116, 3, 116.2, 111.9, 111.8, 84.8, 84.8, 83.7, 83.7, 49.4, 48, 47.9, 47.9, 47.9, 47, 2, 47.2, 47.2, 47.2, 45.4, 45, 37.3, 37.2, 37.1, 37.1, 34.7, 31.5, 30.3, 30, 1, 30.1, 29.1, 27.2, 27.1, 25.4, 25.4, 25.4, 25.3.

[002434] Example 354: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -2-oxopiperidin-3-yl) acetamide

[002435] The compound was prepared analogously to Example 22 from (R) -2- (6- (2,3,6-trifluorophenyl) -2-methyl-3-thioxo-2,5,6 acid, 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002436] 1H NMR (DMSOd6): 8.30 (1 H, d, J = 8.3 Hz), 7.62 (1 H, br s), 7.47 (1 H, m), 7, 18 (1 H, m), 4.42 (1 H, m), 4.23 (1 H, dd, J = 9.6, 11.3 Hz), 4.13 (1 H, m), 3 , 81 (1 H, dd, J = 11.4, 8.1 Hz), 3.47 (2 H, m), 3.42 (3 H, s), 3.29 (1 H, dd, J = 15.7, 9.3 Hz), 3.11 (2 H, m), 2.95 (1 H, dd, J = 16.0, 8.3 Hz), 1.94 (1 H, m ), 1.81 - 1.66 (2 H, m), 1.60 (1 H, m). 13

[002437] C NMR (DMSOd6): 169.5, 167.4, 157, 156.9, 156.9, 156.2, 155.4, 155.3, 155.3, 149.1, 149, 1, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 145.9, 145.8, 128.6, 128.5, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.8, 111.8, 111.8, 111.8, 49.4, 49.2, 41, 34.7, 31.4, 31.3, 29.1, 27.5, 21.

[002438] Example 355: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((1r, 4R) -4-hydroxycyclohexyl) acetamide

[002439] The compound was prepared in an analogous manner to Example 25 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one using DIPEA as base and isolated as a light beige solid.

[002440] 1H NMR (DMSOd6): 7.44 (1 H, dd, J = 6.5, 2.6 Hz), 7.35 (1

H, ddd, J = 8.8, 4.4, 2.7 Hz), 7.16 (1 H, dd, J = 9.8, 8.9 Hz), 4.24 (1 H, d, J = 12.3 Hz), 3.97 (1 H, d, J = 12.2 Hz), 3.65 (1 H, m), 3.56 (2 H, s), 3.52 (1 H, m), 3.48 (3 H, s), 2.81 (1 H, dd, J = 8.3, 4.0 Hz), 1.95 (4 H, m), 1.68 ( 1 H, dd, J = 8.4, 5.6 Hz), 1.34 (4 H, m), 1.18 (1 H, m). 13

[002441] C NMR (DMSOd6): 170.2, 163.3, 161.6, 157.7, 133.8, 131.5, 131.5, 130.9, 130.8, 130.7, 130.7, 130, 129.9, 118.5, 118.4, 118, 70.5, 54.3, 54.3, 49.3, 34.9, 33.3, 32.5, 32, 4, 31.6, 23.3, 22.3.

[002442] Example 356: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-cyclohexylacetamide

[002443] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002444] 1H NMR (DMSOd6): 7.98 (1 H, br d, J = 7.8 Hz), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7 , 22 (1 H, t, J = 9.0 Hz), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, m), 3.80 (1 H, dd, J = 11.6, 7.8 Hz), 3.51 (1 H, m), 3.39 (3 H, m), 3.28 (1 H, br dd, J = 15.9, 9.3 Hz), 2.88 (1 H, br dd, J = 15.8, 7.9 Hz), 1.80-1.40 (6 H, m), 1.32-0.97 ( 6 H, m). 13

[002445] C NMR (DMSOd6): 166.5, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.1, 154.9, 154.9, 129.7, 129.6, 128.3, 118.9, 118.7, 118.6, 116.6, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 49.5, 47.7, 34.7, 33.3, 32.3, 31.4, 31.3, 29.2, 25.2, 24.5.

[002446] Example 357: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N-cyclopropylacetamide

[002447] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002448] 1H NMR (DMSOd6): 8.19 (1 H, d, J = 4.0 Hz), 7.59 (1 H, dd, J = 6.7, 2.6 Hz), 7, 56 (1 H, ddd, J = 8.6, 4.5, 2.6 Hz), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.14 (1 H , d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.46 (2 H, m), 3.34 (3 H, s), 2, 89 (1 H, dd, J = 8.4, 4.1 Hz), 2.64 (1 H, m), 1.69 (1 H, dd, J = 8.3, 5.4 Hz), 1.14 (1 H, t, J = 4.8 Hz), 0.63 (2 H, m), 0.42 (2 H, m).

[002449] 13C NMR (DMSOd6): 168.9, 161.8, 160.1, 156.8, 133, 133, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 116, 52.4, 52.4, 31.5, 31.4, 31, 22.5, 22.1, 20.7, 5.6.

[002450] Example 358: N, N-dimethyl-1- (2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) pyrrolidine-3-carboxamide

[002451] The compound was prepared in an analogous manner to Example 25 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002452] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.18 (1 H, m), 4.43 (1 H, m), 4.24 (1 H, dd, J = 9.5, 11.2 Hz), 3.81 (1 H, dd, J = 11.4, 8.1 Hz), 3.75-3.42 (5.5 H, misc. Mult.) , 3.38 (3 H, s), 3.37 (1 H, m), 3.29 (1.5 H, m), 3.03, 3.02 (3 H, 3 s), 2, 89 (1 H, m), 2.82 (3 H, 4 s), 2.12 (0.5 H, m), 2.05 (0.5 H, m), 1.97 (0.5 H, m), 1.85 (0.5 H, m). 13

[002453] C NMR (DMSOd6): 171.7, 171.7, 171.3, 171.3, 166.1, 166, 166, 166, 156.9, 156.9, 156.2, 156, 2, 155.3, 155.3, 155.3, 149.1, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.2, 119, 118.9, 118.9, 118.8, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.3, 116.2, 116.2, 116.2, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 49.4, 48.6, 48.4, 45.8, 45.8, 45.3, 45.2, 40.2, 40, 38.3, 36.7, 35.1, 35.1, 35, 34.7, 34.7, 31.5, 30.3, 30.3, 30.2, 29.1, 29.1, 29, 27.5.

[002454] Example 359: (5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl- 1- (2 - ((((R) -tetrahydrofuran-3-yl) amino) ethyl ) -5.5a, 6.6a-tetrahydrocyclopropa [3,4] pyrrole [1,2-c] imidazole-3 (2H) -thione

[002455] The compound was prepared analogously to Example 35 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N- ((R) -tetrahydrofuran-3-yl) acetamide (Example 279) and isolated as a beige solid.

[002456] 1H NMR (DMSOd6): 7.58 (1 H, dd, J = 6.6, 2.5 Hz), 7.50 (1 H, m), 7.11 (1 H, t, J = 9.4 Hz), 4.23 (1 H, d, J = 12.2 Hz), 3.95 (2 H, m), 3.83 (1 H, dd, J = 9.2, 5.9 Hz), 3.76 (1 H, td, J = 8.3, 6.4 Hz), 3.65 (1 H, dd, J = 9.2, 4.0 Hz), 3, 52 (4 H, s), 3.04-2.77 (5 H, m), 2.19 (1 H, td, J = 13.4, 7.6 Hz), 1.81 (1 H, m), 1.70 (1 H, dd, J = 8.2, 5.6 Hz), 1.16 (1 H, m). 13

[002457] C NMR (DMSOd6): 163.8, 162.2, 157.5, 134.5, 134.5, 134, 133.9, 132.7, 130.5, 130.4, 121, 119, 118.8, 118, 118, 73.5, 68.3, 59.7, 54.2, 54.1, 47.1, 33.3, 33.2, 32.2, 25.4, 23.3, 22.4.

[002458] Example 360: 2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002459] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a khaki powder.

[002460] 1H NMR (DMSOd6): 11.76 (1 H, s), 8.23 (1 H, d, J = 6.6 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.21 (1 H, m), 4.17 (1 H, dd, J = 11.6, 9.1 Hz), 3.77 (2 H, m), 3.71 (1 H, dd, J = 8.9, 5.9 Hz), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 8.9, 3.7 Hz), 3.25 (1 H, m), 3.25 (2 H, s), 2.88 (1 H, dd, J = 15 , 8, 8.3 Hz), 2.06 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m). 13

[002461] C NMR (DMSOd6): 167.5, 155.2, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143, 6, 143.6, 143.6, 143.6, 128.9, 120.5, 120.3, 120.2, 114.3, 105.9, 105.7, 105.6, 72.4, 66.3, 49.8, 48.4, 35.7, 32, 31.3, 29.2.

[002462] Example 361: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocycloprop acid [3, 4] pyrrole [1,2- c] imidazol-1-yl) acetic

[002463] The compound was prepared in an analogous way to Example 2 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (5-bromo-2-fluorophenyl) - 3-azabicyclo [3.1.0 ] hexane-2-carboxylic. The product was isolated as a light yellow solid.

[002464] 1H NMR (DMSOd6): 11.65 (1 H, br s), 7.56 (2 H, m), 7.24 (1 H, t, J = 9.3 Hz), 4, 08 (1 H, br d, J = 11.9 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.42 (2 H, m), 2.88 (1 H, dd, J = 8.3, 4.2 Hz), 1.66 (1 H, dd, J = 8.1, 5.4 Hz), 1.10 (1 H, m). 13

[002465] C NMR (DMSOd6): 171.1, 161.8, 160.1, 155.9, 132.9, 132.9, 132.3, 132.3, 131.8, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 113.7, 51.6, 51.6, 32.3, 30.5, 22.2, 20.6.

[002466] Example 362: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002467] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-

tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002468] 1H NMR (DMSOd6): 11.75 (1 H, s), 8.22 (1 H, br d, J = 6.6 Hz), 7.61 (1 H, td, J = 8 , 7, 5.6 Hz), 7.22 (1 H, t, J = 8.9 Hz), 4.44 (1 H, quin, J = 8.6 Hz), 4.21 (1 H, m), 4.15 (1 H, dd, J = 11.2, 9.5 Hz), 3.73 (3 H, m), 3.65 (1 H, td, J = 8.2, 5 , 6 Hz), 3.45 (1 H, dd, J = 8.9, 3.7 Hz), 3.24 (2 H, s), 3.21 (1 H, dd, J = 9.0 , 15.6 Hz), 2.84 (1 H, dd, J = 15.6, 8.1 Hz), 2.06 (1 H, m), 1.71 (1 H, m). 13

[002469] C NMR (DMSOd6): 167.5, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 129.1, 118.8, 118.7, 118.5, 116, 116, 115.9, 115.9, 114.2, 113.2, 113.2, 113, 1, 113.1, 72.4, 72.4, 66.3, 49.7, 48.5, 35.6, 32, 31.9, 31.3, 29.3.

[002470] Example 363: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-morpholinoetan-1-one

[002471] The compound was prepared in an analogous manner to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002472] 1H NMR (DMSOd6): 11.69 (1 H, br s), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, t , J = 8.9 Hz), 4.45 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, dd, J = 11.1, 9.6 Hz), 3.73 (1 H, dd, J = 11.4, 7.9 Hz), 3.55 (4 H, m), 3.51 (2 H, s), 3.44 (4 H, m), 3, 22 (1 H, dd, J = 15.8, 9.3 Hz), 2.83 (1 H, dd, J = 15.7, 8.1 Hz).

[002473] C NMR (DMSOd6): 166.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 154.9, 154.9, 129.7, 129.6, 129.3, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114, 113.2, 113.2, 113, 1, 113.1, 66, 66, 48.6, 45.7, 41.7, 35.6, 29.3, 28.8.

[002474] Example 364: N-methyl-N- (tetrahydrofuran-3-yl) -2 - ((R) -3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002475] The compound was prepared in an analogous manner to Example 34 from (R) -2- (3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra- hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002476] 1H NMR (DMSOd6): 11.68 (1 H, m), 7.47 (1 H, qd, J = 9.4, 5.1 Hz), 7.18 (1 H, t, J = 9.5 Hz), 5.08 (0.6 H, m), 4.61 (0.4 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4 , 16 (1 H, m), 3.92 (1 H, m), 3.74 (1 H, dd, J = 11.5, 8.0 Hz), 3.67 (0.8 H, m ), 3.64-3.53 (3 H, m), 3.48 (1.2 H, s), 3.21 (1 H, m), 2.88 (1.8 H, s), 2.83 (1 H, m), 2.72 (1.2 H, s), 2.10 (1 H, m), 1.78 (1 H, m). 13

[002477] C NMR (DMSOd6): 168.3, 167.7, 157, 156.9, 156.9, 155.3, 155.3, 155.2, 155.1, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 129.2, 129.2, 119, 118.9, 118.8, 118.8, 118.7, 118.7, 116.5, 116.4, 116.4, 116.3, 114.3, 114.2, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 69.3, 69.3, 69.3,

67.1, 67.1, 56.5, 52.9, 48.5, 35.6, 30, 29.8, 29.8, 29.7, 29.5, 29.5, 29.3, 29.2, 29.2, 27.6.

[002478] Example 365: N - ((R) -tetrahydro-2H-pyran-3-yl) -2 - ((R) -3-thioxo- 6- (2,3,6-trifluorophenyl) -2 , 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002479] The compound was prepared in an analogous manner to Example 34 from (R) -2- (3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra- hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002480] 1H NMR (DMSOd6): 11.75 (1 H, s), 7.96 (1 H, br d, J = 7.5 Hz), 7.47 (1 H, qd, J = 9 , 4, 5.1 Hz), 7.18 (1 H, m), 4.43 (1 H, quin, J = 8.7 Hz), 4.16 (1 H, m), 3.74 ( 1 H, dd, J = 11.5, 8.1 Hz), 3.65 (3 H, m), 3.33 (1H, m), 3.25 (2 H, s), 3.22 ( 1 H, dd, J = 16.0, 9.5 Hz), 3.09 (1 H, m), 2.85 (1 H, dd, J = 15.7, 8.4 Hz), 1, 80 (1 H, m), 1.66 (1 H, m), 1.45 (2 H, m). 13

[002481] C NMR (DMSOd6): 167.2, 157, 156.9, 155.3, 155.3, 155.1, 149.1, 149, 149, 148.9, 147.6, 147, 5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 129, 118.9, 118.8, 118.8, 118, 7, 116.5, 116.4, 116.4, 116.3, 114.4, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 70, 2, 67, 48.5, 45.1, 35.6, 31.4, 29.3, 28.6, 23.9.

[002482] Example 366: (R) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -1-morpholinoetan-1-one

[002483] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[002484] 1H NMR (DMSOd6): 11.70 (1 H, s), 7.47 (1 H, qd, J = 9.4, 4.9 Hz), 7.18 (1 H, m) , 4.44 (1 H, quin, J = 8.7 Hz), 4.17 (1 H, dd, J = 11.1, 9.5 Hz), 3.74 (1 H, dd, J = 11.6, 8.1 Hz), 3.55 (4 H, m), 3.51 (2 H, s), 3.45 (4 H, m), 3.22 (1 H, dd, J = 15.7, 9.2 Hz), 2.85 (1 H, dd, J = 15.8, 8.3 Hz).

[002485] 13C NMR (DMSOd6): 166.8, 157, 157, 156.9, 156.9, 155.4, 155.3, 155.3, 155.2, 149.1, 149, 149, 148.9, 147.6, 147.5, 147.4, 147.4, 147.3, 146, 145.9, 145.9, 145.8, 129.2, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 114.1, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 66, 66, 48.5, 45.7, 41.7, 35.6, 29.2, 28.8.

[002486] Example 367: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002487] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002488] 1H NMR (DMSOd6): 8.11 (1 H, d, J = 7.6 Hz), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7, 22 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.4, 9.3 Hz), 3.80 ( 3 H, m), 3.75 (1 H, m), 3.42 (2 H, d, J = 2.2 Hz), 3.40 (3 H, s), 3.33 (2 H, m), 3.29 (1 H, dd, J = 9.2, 15.8 Hz), 2.89 (1 H, dd, J = 15.8, 8.1 Hz), 1.69 (2 H, dt, J = 12.7, 2.2 Hz), 1.38 (2 H, m). 13

[002489] C NMR (DMSOd6): 166.8, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.7, 118.6, 116.5, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 65.8, 49.5, 45.2, 34.7, 32.4, 32.4, 31.5, 31.3, 29.2.

[002490] Example 368: 2 - ((R) -6- (2,3,6-trifluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002491] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[002492] 1H NMR (DMSOd6): 11.75 (1 H, s), 8.22 (1 H, d, J = 6.6 Hz), 7.47 (1 H, qd, J = 9, 5, 5.1 Hz), 7.18 (1 H, tdd, J = 9.6, 9.6, 3.7, 1.8 Hz), 4.43 (1 H, quin, J = 8, 7 Hz), 4.21 (1 H, tt, J = 10.2, 3.9 Hz), 4.16 (1 H, dd, J = 11.4, 9.3 Hz), 3.73 ( 3 H, m), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 8.9, 3.6 Hz), 3, 24 (2 H, s), 3.22 (1 H, m), 2.86 (1 H, dd, J = 15.8, 8.4 Hz), 2.06 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m). 13

[002493] C NMR (DMSOd6): 167.5, 157, 156.9, 156.9, 155.4, 155.3, 155.3, 155.1, 149.1, 149, 149, 148, 9, 147.6, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 129.1, 118.9, 118.8, 118.7, 118.7, 116.5, 116.4, 116.4, 116.3, 114.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 72.4, 66.3, 49.8, 48.5, 35.6, 32, 31.3, 29.3.

[002494] Example 369: 2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[002495] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a khaki powder.

[002496] 1H NMR (DMSOd6): 11.76 (1 H, br s), 8.23 (1 H, br d, J = 6.6 Hz), 7.85 (1 H, m), 4 , 48 (1 H, quin, J = 8.5 Hz), 4.21 (1 H, m), 4.17 (1 H, dd, J = 11.7, 9.2 Hz), 3.77 (2 H, m), 3.71 (1 H, dd, J = 8.9, 6.0 Hz), 3.65 (1 H, td, J = 8.3, 5.5 Hz), 3 , 45 (1 H, dd, J = 8.9, 3.7 Hz), 3.25 (2 H, s), 3.25 (1 H, dd, J = 9.4, 15.8 Hz) , 2.88 (1 H, dd, J = 15.8, 8.1 Hz), 2.06 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m). 13

[002497] C NMR (DMSOd6): 167.5, 155.2, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143, 7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.3, 105.8, 105.7, 105.5, 72.4, 66.3, 49.8, 48.4, 35.7, 31.9, 31.3, 29.2.

[002498] Example 370: 2 - ((R) -6- (2,3,6-trifluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c ] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[002499] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[002500] 1H NMR (DMSOd6): 11.75 (1 H, br s), 8.22 (1 H, br d, J = 6.6 Hz), 7.47 (1 H, qd, J = 9.4, 4.9 Hz), 7.18 (1 H, m), 4.43 (1 H, quin, J = 8.7 Hz), 4.21 (1 H, m), 4.16 (1 H, m), 3.82-3.69 (3 H, m), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd , J = 8.9, 3.7 Hz), 3.24 (2 H, s), 3.22 (1 H, m), 2.86 (1 H, dd, J = 15.7, 8, 5 Hz), 2.06 (1 H, m), 1.71 (1 H, m).

[002501] 13C NMR (DMSOd6): 167.5, 157, 157, 156.9, 156.9, 155.4, 155.3, 155.3, 155.1, 149.1, 149, 149, 149, 148.9, 147.6, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 129.1, 118.9, 118.8, 118.7, 118.7, 116.5, 116.4, 116.4, 116.3, 114.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 72.4, 66.3, 49.8, 48.5, 35.6, 32, 31.3, 29.3.

[002502] Example 371: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (1-methyl-6-oxopiperidin-3-yl) acetamide

[002503] The compound was prepared in an analogous manner to Example 22 from (R) -2- (6- (2,3,6-trifluorophenyl) -2-methyl-3-thioxo-2,5,6 acid, 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002504] 1H NMR (DMSOd6): 8.35 (1 H, d, J = 7.7 Hz), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7, 18 (1 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4.24 (1 H, dd, J = 11.2, 9.4 Hz), 4.04 ( 1 H, m), 3.81 (1 H, dd, J = 11.5, 8.0 Hz), 3.47 (2 H, m), 3.40 (4 H, m), 3.30 (1 H, dd, J = 9.3, 15.8 Hz), 3.07 (1 H, ddd, J = 12.1, 6.9, 2.2 Hz), 2.91 (1 H, dd, J = 15.8, 8.2 Hz), 2.77 (3 H, 2 s), 2.28 (2 H, m), 1.85 (1 H, m), 1.75 (1 H, m). 13

[002505] C NMR (DMSOd6): 167.7, 167.6, 157, 156.9, 156.2, 155.3, 155.3, 149.1, 149, 149, 148.9, 147, 6, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.4, 118.9, 118.8, 118.8, 118.7, 116.5, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 52.9, 49.5, 43.4, 43.4, 34.7, 33.9, 31.5, 31.1, 31.1, 29.2, 29, 29, 26, 1.

[002506] Example 372: (R) -N-methyl-2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H -pyrrolo [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002507] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002508] 1H NMR (DMSOd6): 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7.18 (1 H, m), 4.45 (1.6 H, m), 4.24 (1 H, br t, J = 10.3 Hz), 3.90 (2.4 H, m), 3.82 (1.8 H, m), 3.72 (1 , 2 H, m), 3.40 (1.8 H, m), 3.30 (1.2 H, m), 2.96-2.84 (2.8 H, m), 2.72 (1.2 H, s), 1.84-1.63 (2 H, m), 1.58 (0.8 H, m), 1.41 (1.2 H, m). 13

[002509] C NMR (DMSOd6): 167.7, 167.5, 157, 156.9, 156.9, 156.9, 156.2, 156.2, 155.3, 155.3, 149, 1, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 128.2, 128.2, 119, 118.9, 118.9, 118.8, 116.8, 116.6, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 66.5, 66.3, 53, 49.7, 49.4, 34.8, 31.5, 31.5, 30.2, 30.2, 29.9, 29.5, 29.2, 29.2, 29.2, 29, 27.1.

[002510] Example 373: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[002511] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (3-chloro- 2,6-difluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002512] 1H NMR (DMSOd6): 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.21 (1 H, t, J = 9.5 Hz), 4, 45 (1.6 H, m), 4.23 (1 H, br t, J = 10.3 Hz), 3.98-3.84 (2.4 H, m), 3.84-3, 76 (1.8 H, m), 3.72 (1.2 H, m), 3.43-3.23 (3 H, m), 3.35 (3 H, s), 2.89 ( 1.8 H, s), 2.86 (1 H, m), 2.72 (1.2 H, s), 1.83-1.64 (2 H, m), 1.58 (0, 8 H, br t, J = 10.9 Hz), 1.40 (1.2 H, m). 13

[002513] C NMR (DMSOd6): 167.7, 167.5, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.2, 128.2, 119, 118.9, 118.8, 118.8, 118.7, 118.7, 116.7, 116.5, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 66.5, 66.3, 53, 49.7, 49.5, 34, 8, 31.5, 31.5, 30.2, 30.2, 29.9, 29.5, 29.2, 29.2, 29.2, 29.1, 27.1.

[002514] Example 374: N-methyl-2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H -pyrrolo [1,2-c] imidazol-1-yl) -N- (tetrahydrofuran-3-yl) acetamide

[002515] The compound was prepared in an analogous manner to Example 34 from (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6 acid, 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002516] 1H NMR (DMSOd6): 7.47 (1 H, qd, J = 9.4, 4.9 Hz), 7.18 (1 H, m), 5.09 (0.6 H, m), 4.65 (0.4 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4.24 (1 H, m), 3.92 (1 H, m ), 3.82 (1.8 H, m), 3.71 (2 H, s), 3.65-3.52 (2.2 H, m), 3.27 (1 H, m), 2.93 (1.8 H, s), 2.87 (1 H, m), 2.74 (1.2 H, s), 2.20 (0.4 H, m), 2.10 ( 0.6 H, m), 1.85 (0.4 H, m), 1.77 (0.6 H, m). 13

[002517] C NMR (DMSOd6): 168.2, 167.6, 157, 156.9, 156.2, 156.2, 155.3, 155.3, 149.1, 149, 149, 148, 9, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.9, 145.8, 128.2, 128.1, 118.9, 118.8, 118.8, 118.7, 116.6, 116.5, 116.4, 116.4, 116.3, 112, 111.8, 69.4, 69.4, 69.3, 69.2, 67.1, 67.1, 56.6, 56.5, 53, 49.4, 34.8, 31.5, 31.5, 30, 29, 8, 29.7, 29.7, 29.4, 29.4, 29.3, 29.1, 29.1, 27.6.

[002518] Example 375: N-methyl-2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (tetrahydrofuran-3-yl) acetamide

[002519] The compound was prepared analogously to Example 34 from (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5-acid, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a yellowish powder.

[002520] 1H NMR (DMSOd6): 7.86 (1 H, m), 5.09 (0.6 H, m), 4.65 (0.4 H, m), 4.48 (1 H , quin, J = 8.4 Hz), 4.25 (1 H, dd, J = 11.3, 9.4 Hz), 3.92 (1 H, m), 3.84 (1.8 H , m), 3.76-3.65 (2 H, s), 3.62 (1.2 H, m), 3.56 (1 H, m), 3.35 (3 H, 2 s) , 3.29 (1 H, m), 2.93 (1.8 H, m), 2.89 (1 H, m), 2.74 (1.2 H, s), 2.20 (0 , 4 H, m), 2.10 (0.6 H, m), 1.86 (0.4 H, m), 1.78 (0.6 H, m). 13

[002521] C NMR (DMSOd6): 168.2, 167.6, 167.6, 156.2, 146.4, 146.4, 146.4, 146.4, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 143.7, 143.7, 143, 7, 143.6, 143.6, 143.6, 143.6, 128.1, 127.9, 120.5, 120.4, 120.3, 116.6, 116.5, 105.9, 105.7, 105.6, 69.4, 69.4, 69.3, 69.2, 67.1, 67, 56.6, 56.5, 53, 49.4, 34.9, 31, 5, 31.5, 30, 29.8, 29.7, 29.7, 29.4, 29.4, 29.3, 29.1, 29, 27.6, 27.6.

[002522] Example 376: (R) -N- (tetrahydro-2H-pyran-4-yl) -2- (3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002523] The compound was prepared in an analogous manner to Example 32 from (R) -2- (3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra- hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002524] 1H NMR (DMSOd6): 11.75 (1 H, s), 7.98 (1 H, br d, J = 7.5 Hz), 7.47 (1 H, qd, J = 9 , 4, 4.9 Hz), 7.18 (1 H, m), 4.43 (1 H, quin, J = 8.7 Hz), 4.16 (1 H, dd, J = 11.2 , 9.5 Hz), 3.80 (2 H, dt, J = 11.3, 3.3 Hz), 3.73 (2 H, m), 3.31 (2 H, m), 3, 23 (2 H, s), 3.22 (1 H, dd, J = 9.1, 15.5 Hz), 2.86 (1 H, dd, J = 15.8, 8.3 Hz), 1.68 (2 H, m), 1.37 (2 H, m). 13

[002525] C NMR (DMSOd6): 166.8, 157, 156.9, 155.4, 155.3, 155.1, 149.1, 149, 149, 148.9, 147.6, 147, 5, 147.5, 147.5, 147.4, 147.4, 145.9, 145.9, 145.9, 145.8, 129, 118.9, 118.8, 118.8, 118, 7, 116.5, 116.4, 116.4, 116.3, 114.4, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 65, 8, 48.5, 45.2, 35.6, 32.4, 31.5, 29.4.

[002526] Example 377: (R) -N- (tetrahydro-2H-pyran-4-yl) -2- (3-thioxo-6- (2,3,5,6-tetrafluorophenyl) -2,5 , 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002527] The compound was prepared analogously to Example 32 from (R) -2- (3-thioxo-6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as beige powder.

[002528] 1H NMR (DMSOd6): 11.76 (1 H, s), 7.98 (1 H, br d, J = 7.5 Hz), 7.85 (1 H, m), 4, 48 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.4, 9.3 Hz), 3.89-3.67 (4 H, m), 3.32 (2 H, m), 3.25 (1 H, dd, J = 9.2, 16.1 Hz), 3.24 (2 H, s), 2.88 (1 H, dd, J = 8.1, 15.8 Hz), 1.67 (2 H, m), 1.37 (2 H, m). 13

[002529] C NMR (DMSOd6): 166.8, 155.1, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 145.4, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143, 7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.9, 120.5, 120.4, 120.3, 114.4, 105.9, 105.7, 105.6, 65.8, 48.4, 45.2, 35.7, 32.4, 31.5, 29.3.

[002530] Example 378: (R) -N-methyl-2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002531] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a beige powder.

[002532] 1H NMR (DMSOd6): 11.71 (1 H, br s), 7.85 (1 H, m), 4.47 (1.6 H, m), 4.18 (1 H, br t, J = 10.3 Hz), 3.88 (2.4 H, m), 3.78 (1 H, m), 3.58, 3.49 (2 H, 2 s), 3, 33 (2 H, m), 3.25 (1 H, m), 2.84 (2.8 H, s), 2.70 (1.2 H, s), 1.85-1.62 ( 2 H, m), 1.51 (0.8 H, m), 1.38 (1.2 H, m). 13

[002533] C NMR (DMSOd6): 167.7, 167.6, 155.1, 146.5, 146.4, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144, 9, 144.8, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 129.1, 129, 120.5, 114.5, 114.3, 105.9, 105.7, 105.5, 66.5, 66.3, 53, 49.6, 48.5, 35.8, 30.3, 30.2, 30, 29.6, 29.3, 29.2, 29.2, 27.

[002534] Example 379: (R) -N-methyl-2- (6- (2,3,6-trifluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002535] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,6-trifluorophenyl) -3-thioxo - 3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as a cream powder.

[002536] 1H NMR (DMSOd6): 11.69 (1 H, s), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7.18 (1 H, m) , 4.44 (1.6 H, m), 4.17 (1 H, br t, J = 10.3 Hz), 3.88 (2.4 H, m), 3.74 (1 H, dd, J = 11.3, 8.2 Hz), 3.57 (0.8 H, m), 3.49 (1.2 H, m), 3.40-3.30 (2 H, m ), 3.22 (1 H, m), 2.84 (2.8 H, m), 2.70 (1.2 H, s), 1.83-1.62 (2 H, m), 1.52 (0.8 H, m), 1.37 (1.2 H, m). 13

[002537] C NMR (DMSOd6): 167.7, 167.6, 156.9, 156.9, 155.3, 155.3, 155.1, 155.1, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 129.2, 129.2, 119, 119, 118, 9, 118.9, 118.9, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.3, 114.5, 114.3, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.8, 66.5, 66.2, 53, 49.6, 48.5, 35.6, 30.3, 30.2, 30, 29.6, 29.4, 29.2, 27.

[002538] Example 380: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[002539] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (6- (3-chloro-2,6-difluorophenyl) -3 - thioxo-3,5,6,7-tetrahydro-2H-pyrrolo [1,2-c] imidazol-1-yl) ethanone and isolated as an off-white solid.

[002540] 1H NMR (DMSOd6): 11.69 (1 H, br s), 7.61 (1 H, td, J = 8.6, 5.6 Hz), 7.21 (1 H, t , J = 9.5 Hz), 4.45 (1.6 H, m), 4.16 (1 H, br t, J = 10.3 Hz), 3.88 (2.4 H, m) , 3.73 (1 H, dd, J = 11.4, 8.0 Hz), 3.57 (1.2 H, m), 3.49 (1.8 H, m), 3.39 ( 1 H, m), 3.34 (1 H, m), 3.31 (1 H, dd, J = 4.5, 2.2 Hz), 3.22 (1 H, m), 2.84 (2 H, s), 2.70 (1 H, s), 1.71 (2 H, m), 1.52 (1 H, br t, J = 12.5 Hz), 1.37 (1 H, m). 13

[002541] C NMR (DMSOd6): 167.7, 167.6, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.1, 155, 154, 9, 154.9, 129.7, 129.6, 129.3, 129.2, 119, 118.9, 118.8, 118.8, 118.7, 118.7, 116.1, 116, 115.9, 115.9, 114.4, 114.2, 113.3, 113.2, 113.1, 113.1, 66.5, 66.5, 66.2, 53, 49.6, 48.6, 35.6, 30.3, 30.2, 30, 29.6, 29.4, 29.2, 29.2, 27.

[002542] Example 381: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[002543] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo- 2,3,5,5a , 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a yellow solid .

[002544] 1H NMR (DMSOd6): 11.63 (1 H, br d, J = 13.5 Hz), 7.63 (1 H, m), 7.20 (1 H, br t, J = 9.2 Hz), 4.49 (0.6 H, m), 4.18-3.92 (1.8 H, m), 3.89 (2 H, m), 3.72 (0, 6 H, m), 3.70-3.48 (2 H, m), 3.45-3.30 (2 H, m), 2.90-2.63 (4 H, m), 1, 84-1.15 (6 H, m). 13

[002545] C NMR (DMSOd6): 167.7, 167.6, 161.2, 159.6, 157.8, 157.7, 156.1, 156.1, 155.9, 155.8, 131.5, 131.3, 130.3, 130.3, 130.3, 130.3, 130.2, 117.1, 116.9, 115.7, 115.7, 115.6, 115, 6, 114.5, 114.2, 112.9, 112.9, 112.8, 66.5, 66.5, 66.3, 64.9, 52.9, 51.4, 51.4, 49.6, 49.4, 30.2, 29.6, 29.3, 29.2, 29.2, 27.1, 26.5, 26.4, 21.8, 21.7, 21, 3, 21.2.

[002546] Example 382: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[002547] The compound was prepared in an analogous way to Example 34 from (S) -2- (2-methyl-3-thioxo-6- (3-bromo-2,6-difluorophenyl) - 2.5 acid, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002548] 1H NMR (DMSOd6): 8.11 (1 H, br d, J = 7.5 Hz), 7.72 (1 H, td, J = 8.5, 5.8 Hz), 7 , 17 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, m), 3.79 (1 H, dd, J = 11.6 , 7.6 Hz), 3.65 (3 H, m), 3.44 (2 H, m), 3.39 (3 H, s), 3.33 (1H, m), 3.28 ( 1 H, dd, J = 15.8, 9.4 Hz), 3.11 (1 H, m), 2.87 (1 H, dd, J = 15.8, 7.9 Hz), 1, 80 (1 H, m), 1.66 (1 H, m), 1.46 (2 H, m). 13

[002549] C NMR (DMSOd6): 167.3, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.1, 155.9, 155.9, 132.5, 132.4, 128.4, 118.8, 118.7, 118.6, 116.4, 113.8, 113.8, 113.6, 113.6, 113.6, 112, 3, 112.1, 104.1, 104.1, 103.9, 103.9, 70.1, 67, 49.6, 45.1, 34.8, 31.5, 31.2, 29, 2, 28.5, 23.8.

[002550] Example 383: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[002551] The compound was prepared analogously to Example 34 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5-acid, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white solid.

[002552] 1H NMR (DMSOd6): 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m), 5.09 (0.6 H, m), 4.65 (0.4 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, m), 3.91 (1 H, m ), 3.81 (1.8 H, m), 3.75-3.65 (2 H, m), 3.65-3.59 (1.2 H, m), 3.56 (1 H , m), 3.35 (3 H, 2 s), 3.26 (1 H, m), 2.93 (1.8 H, s), 2.85 (1 H, m), 2.74 (1.2 H, s), 2.20 (0.4 H, m), 2.10 (0.6 H, m), 1.85 (0.4 H, m), 1.77 (0 , 6 H, m). 13

[002553] C NMR (DMSOd6): 168.2, 167.6, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.2, 156.2, 154.9, 154.9, 129.7, 129.6, 128.3, 128.1, 118.9, 118.8, 118.6, 116.5, 116.4, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 69.4, 69.4, 69.3, 69.2, 67.1, 67, 56.6, 56.5, 53, 49.5, 34.8, 31.5, 31.5, 29.9, 29.8, 29.7, 29.7, 29.4, 29.4, 29.3, 29.2, 29.1, 27.6.

[002554] Example 384: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[002555] The compound was prepared analogously to Example 34 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white solid.

[002556] 1H NMR (DMSOd6): 11.68 (1 H, m), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.21 (1 H, m) , 5.08 (0.6 H, m), 4.61 (0.4 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, m ), 3.91 (1 H, m), 3.73 (1 H, dd, J = 11.6, 7.8 Hz), 3.66 (0.8 H, dd, J = 7.3, 5.9 Hz), 3.63-3.52 (3 H, m), 3.48 (1.2 H, s), 3.21 (1 H, m), 2.88 (1.8 H , d, J = 1.5 Hz), 2.82 (1 H, m), 2.72 (1.2 H, s), 2.22 - 2.02 (1 H, m), 1.88 -1.67 (1 H, m).

[002557] 3C NMR (DMSOd6): 168.2, 167.7, 160.1, 160.1, 158.5, 158.5, 156.5, 155.1, 155.1, 154.9, 154.9, 129.7, 129.6, 129.3, 129.2, 118.9, 118.9, 118.9, 118.8, 118.8, 118.7, 118.6, 118, 6, 116.1, 116, 115.9, 115.9, 114.3, 114.2, 114.2, 113.3, 113.2, 113.1, 113.1, 69.3, 69, 3, 69.3, 67.1, 67.1, 67, 56.5, 52.9, 48.6, 35.6, 30, 29.8, 29.8, 29.8, 29.7, 29.5, 29.5, 29.3, 29.2, 27.6.

[002558] Example 385: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - (((S) -tetrahydrofuran-3-yl) acetamide

[002559] The compound was prepared analogously to Example 32 from (R) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002560] 1H NMR (DMSOd6): 8.37 (1 H, br d, J = 6.6 Hz), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7 , 22 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (2 H, m), 3.78 (2 H, m), 3.72 ( 1 H, dd, J = 9.0, 5.9 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, dd, J = 8 , 9, 3.5 Hz), 3.43 (2 H, s), 3.40 (3 H, s), 3.29 (1 H, dd, J = 15.9, 9.5 Hz), 2.89 (1 H, dd, J = 15.8, 8.1 Hz), 2.08 (1 H, m), 1.71 (1 H, m). 13

[002561] C NMR (DMSOd6): 167.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.7, 118.6, 116.4, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 72.3, 66.3, 49.8, 49.5, 34.7, 32, 31.5, 31.1, 29.2.

[002562] Example 386: N - ((R) -tetrahydro-2H-pyran-3-yl) -2 - ((R) -3-thioxo-6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002563] The compound was prepared in an analogous manner to Example 34 from (R) -2- (3-thioxo-6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a light beige powder.

[002564] 1H NMR (DMSOd6): 11.76 (1 H, s), 7.97 (1 H, br d, J = 7.5 Hz), 7.85 (1 H, m), 4, 48 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.4, 9.3 Hz), 3.77 (1 H, dd, J = 11.7 , 7.8 Hz), 3.65 (3 H, m), 3.34 (1 H, m), 3.25 (2 H, s), 3.25 (1 H, dd, J = 9, 5, 15.6 Hz), 3.09 (1 H, m), 2.88 (1 H, br dd, J = 15.7, 8.1 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.45 (2 H, m). 13

[002565] C NMR (DMSOd6): 167.2, 155.1, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144, 7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.8, 120.5, 120.4, 120.3, 114.4, 105.9, 105.7, 105.5, 70.2, 67, 48.4, 45.1, 35.7, 31.4, 29.2, 28.6, 23.9.

[002566] Example 387: 2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((((S) -tetrahydrofuran-2-yl) methyl) acetamide

[002567] The compound was prepared analogously to Example 32 from (R) -2- (6- (2,3,5,6-tetrafluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a light beige powder.

[002568] 1H NMR (DMSOd6): 8.18 (1 H, t, J = 5.7 Hz), 7.86 (1 H, m), 4.48 (1 H, quin, J = 8, 5 Hz), 4.24 (1 H, dd, J = 11.6, 9.2 Hz), 3.83 (2 H, m), 3.73 (1 H, m), 3.59 (1 H, m), 3.46 (2 H, m), 3.40 (3 H, s), 3.31 (1 H, dd, J = 9.5, 16.0 Hz), 3.16 ( 1 H, m), 3.10 (1 H, m), 2.93 (1 H, dd, J = 15.9, 8.0 Hz), 1.92-1.72 (3 H, m) , 1.46 (1 H, m). 13

[002569] C NMR (DMSOd6): 167.8, 156.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144, 6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 128.2, 120.4, 120.3, 120.2, 116.5, 105.9, 105.7, 105.6, 77, 67.1, 49.4, 42.9, 34.9, 31.4, 31.2, 29, 28.4, 25.1.

[002570] Example 388: N- (1-methyl-2-oxopyrrolidin-3-yl) -2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2 , 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002571] The compound was prepared analogously to Example 22 from (R) -2- (6- (2,3,6-trifluorophenyl) -2-methyl-3-thioxo-2,5,6 acid, 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002572] 1H NMR (DMSOd6): 8.40 (1 H, dd, J = 14.0, 8.1 Hz), 7.48 (1 H, qd, J = 9.3, 5.0 Hz ), 7.19 (1 H, m), 4.42 (1 H, m), 4.33 (1 H, m), 4.23 (1 H, m), 3.82 (1 H, dd , J = 11.4, 8.2 Hz), 3.53-3.43 (2 H, m), 3.42 (3 H, m), 3.37-3.28 (1 H, m) , 3.26 (2 H, m), 2.93 (1 H, m), 2.73 (3 H, 2 s), 2.27 (1 H, m), 1.76 (1 H, m ). 13

[002573] C NMR (DMSOd6): 171.3, 167.7, 157, 156.9, 156.3, 155.4, 155.3, 149.1, 149.1, 149, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 145.9, 145.9, 145.9, 145.8, 128.7, 128.6, 118.8, 118, 7, 118.7, 118.6, 118.6, 118.5, 116.5, 116.5, 116.5, 116.5, 116.4, 116.4, 116.3, 116.3, 116.2, 116.1, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 111.8, 50.2, 50.1, 49.4, 45.3, 34.8, 31.4, 31.3, 31.3, 29.7, 29.1, 25.7, 25.7.

[002574] Example 389: 2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((S) -1-methyl-5-oxopyrrolidin-3-yl) acetamide

[002575] The compound was prepared in an analogous way to Example 22 from (R) -2- (6- (2,3,6-trifluorophenyl) -2-methyl-3-thioxo-2,5,6 acid, 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002576] 1H NMR (DMSOd6): 8.54 (1 H, br d, J = 6.6 Hz), 7.48 (1 H, qd, J = 9.4, 5.0 Hz), 7 , 19 (1 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4.28 (1 H, m), 4.23 (1 H, m), 3.81 ( 1 H, dd, J = 11.4, 8.0 Hz), 3.61 (1 H, dd, J = 10.3, 7.0 Hz), 3.44 (2 H, d, J = 3 , 2 Hz), 3.40 (3 H, s), 3.30 (1 H, br dd, J = 15.8, 9.4 Hz), 3.11 (1 H, dd, J = 10, 2, 3.6 Hz), 2.90 (1 H, br dd, J = 15.8, 8.3 Hz), 2.70 (3 H, s), 2.57 (1 H, dd, J = 16.8, 8.6 Hz), 2.11 (1 H, dd, J = 16.9, 4.1 Hz). 13

[002577] C NMR (DMSOd6): 171.6, 167.7, 157, 156.9, 156.3, 155.3, 155.3, 149.1, 149.1, 149, 149, 147, 6, 147.5, 147.4, 145.9, 145.8, 128.5, 118.9, 118.8, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 116.2, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 55.1, 49.5, 42.4, 36.8, 34.7, 31.5, 31.1, 29.1, 28.9.

[002578] Example 390: (R) -1- (2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra- hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) pyrrolidine-3-carbonitrile

[002579] The compound was prepared analogously to Example 25 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002580] 1H NMR (DMSOd6): 7.48 (1 H, qd, J = 9.4, 5.0 Hz), 7.19 (1 H, m), 4.44 (1 H, m) , 4.25 (1 H, m), 3.91-3.38 (8 H, m), 3.38 (3 H, s), 3.29 (1 H, m), 2.90 (1 H, m), 2.32 (0.5 H, m), 2.23 (1 H, m), 2.10 (0.5 H, m). 13

[002581] C NMR (DMSOd6): 166.6, 166.4, 157, 156.9, 156.9, 156.3, 155.3, 155.3, 155.3, 155.3, 149, 1, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.4, 128.3, 121.1, 120.9, 118.9, 118.9, 118.8, 118.8, 118.8, 118.8, 118.7, 118.7, 116, 5, 116.4, 116.4, 116.3, 115.9, 115.9, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 49, 5, 48.7, 48.6, 44.8, 44.6, 34.7, 31.5, 30.2, 30.1, 29.6, 29.1, 28.1, 28, 26, 5.

[002582] Example 391: 2 - ((R) -2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((((R) -tetrahydrofuran-2-yl) methyl) acetamide

[002583] The compound was prepared analogously to Example 32 from (R) -2- (6- (2,3,5,6-terafluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002584] 1H NMR (DMSOd6): 8.18 (1 H, t, J = 5.7 Hz), 7.86 (1 H, m), 4.48 (1 H, quin, J = 8, 5 Hz), 4.24 (1 H, dd, J = 11.6, 9.2 Hz), 3.83 (2 H, m), 3.73 (1 H, m), 3.59 (1 H, m), 3.46 (2 H, m), 3.40 (3 H, s), 3.31 (1 H, dd, J = 9.5, 16.0 Hz), 3.16 ( 1 H, m), 3.10 (1 H, m), 2.93 (1 H, dd, J = 15.9, 8.0 Hz), 1.92-1.72 (3 H, m) , 1.46 (1 H, m). 13

[002585] C NMR (DMSOd6): 167.8, 156.2, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143, 7, 143.7, 143.6, 143.6, 143.6, 128.2, 120.4, 120.3, 120.2, 116.5, 105.9, 105.7, 105.6, 77, 67.1, 49.4, 42.9, 34.9, 31.5, 31.2, 29, 28.4, 25.1.

[002586] Example 392: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N - ((R) -tetrahydrofuran-3-yl) acetamide

[002587] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo- 2,3,5,5a , 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a khaki solid .

[002588] 1H NMR (DMSOd6): 11.69 (1 H, s), 8.26 (1 H, br d, J = 6.6 Hz), 7.63 (1 H, td, J = 8 , 6, 5.6 Hz), 7.21 (1 H, t, J = 9.2 Hz), 4.24 (1 H, m), 4.03 (1 H, d, J = 12.2 Hz), 3.78 (1 H, q, J = 7.4 Hz), 3.73 (2 H, m), 3.67 (1 H, td, J = 8.2, 5.6 Hz) , 3.48 (1 H, dd, J = 8.9, 3.7 Hz), 3.31 (2 H, m), 2.72 (1 H, dd, J = 8.3, 4.5 Hz), 2.08 (1 H, dq, J = 12.7, 7.6 Hz), 1.74 (1 H, m), 1.66 (1 H, dd, J = 8.1, 5 , 5 Hz), 1.24 (1 H, t, J = 4.9 Hz). 13

[002589] C NMR (DMSOd6): 167.6, 161.2, 161.2, 159.6, 159.5, 157.8, 157.7, 156.1, 156.1, 155.8, 131.3, 130.3, 130.2, 117.2, 117.1, 117.1, 116.9, 115.7, 115.7, 115.6, 115.6, 114.3, 112, 9, 112.9, 112.8, 112.8, 72.4, 66.3, 51.4, 49.8, 32, 31.3, 26.3, 21.6, 21.6, 21, 3.

[002590] Example 393: (R) -N- (oxetan-3-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002591] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a beige powder.

[002592] 1H NMR (DMSOd6): 11.77 (1 H, s), 8.72 (1 H, br d, J = 6.5 Hz), 7.85 (1 H, m), 4, 76 (1 H, m), 4.69 (2 H, t, J = 6.8 Hz), 4.48 (1 H, quin, J = 8.5 Hz), 4.41 (2 H, t , J = 6.0 Hz), 4.17 (1 H, dd, J = 11.2, 9.5 Hz), 3.77 (1 H, dd, J = 11.6, 7.9 Hz) , 3.28 (2 H, s), 3.25 (1 H, br dd, J = 15.9, 9.5 Hz), 2.88 (1 H, br dd, J = 15.8, 8 , 0 Hz). 13

[002593] C NMR (DMSOd6): 167.4, 155.3, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143, 6, 143.6, 143.6, 129.2, 120.4, 120.3, 120.2, 114, 105.9, 105.7, 105.6, 77, 48.4, 44.1, 35.7, 31.2, 29.2.

[002594] Example 394: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[002595] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (2,3,5,6- tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a white powder.

[002596] 1H NMR (DMSOd6): 8.85 (1 H, br d, J = 6.6 Hz), 7.86 (1 H, m), 4.78 (1 H, m), 4, 70 (2 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.41 (2 H, t, J = 6.3 Hz), 4.26 (1 H, dd , J = 11.5, 9.3 Hz), 3.86 (1 H, dd, J = 11.7, 7.7 Hz), 3.48 (2 H, m), 3.39 (3 H , m), 3.33 (1 H, dd, J = 9.5, 16 Hz), 2.94 (1 H, dd, J = 15.8, 7.9 Hz). 13

[002597] C NMR (DMSOd6): 167.4, 156.3, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 143.7, 143, 7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.4, 120.4, 120.3, 120.2, 116.1, 105.9, 105.7, 105.6, 77, 49.4, 44.2, 34.9, 31.5, 31, 29.

[002598] Example 395: 2 - ((R) -6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((((S) -tetrahydrofuran-2-yl) methyl) acetamide

[002599] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (6- (2,3,5,6-tetrafluorophenyl) -3 -tioxo- 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a beige powder.

[002600] 1H NMR (DMSOd6): 11.75 (1 H, s), 8.03 (1 H, br t, J = 5.6 Hz), 7.85 (1 H, m), 4, 48 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.2, 9.5 Hz), 3.81 (1 H, m), 3.77 ( 1 H, dd, J = 11.5, 7.8 Hz), 3.72 (1 H, m), 3.58 (1 H, m), 3.26 (2 H, s), 3.24 (1 H, m), 3.16 (1 H, m), 3.09 (1 H, m), 2.88 (1 H, br dd, J = 15.8, 8.1 Hz), 1 , 94-1.68 (3 H, m), 1.46 (1 H, m). 13

[002601] C NMR (DMSOd6): 167.7, 155.2, 146.4, 146.4, 146.3, 146.3, 146.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 143.7, 143.7, 143.6, 143.6, 128, 9, 120.4, 120.3, 120.2, 114.4, 105.9, 105.7, 105.6, 77, 67.1, 48.4, 42.9, 35.7, 31, 4, 29.2, 28.5, 25.1.

[002602] Example 396: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3 , 4] pyrrolo [1,2-c] imidazol-1-yl) - N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[002603] The compound was prepared analogously to Example 221, step 2, from acid 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -3-thioxo-2, 3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a yellow solid.

[002604] 1H NMR (DMSOd6): 11.62 (1 H, br s), 7.63 (1 H, td, J = 8.6, 5.9 Hz), 7.20 (1 H, br t, J = 8.9 Hz), 5.11 (0.6 H, br s), 4.67 (0.4 H, m), 4.04 (1 H, br d, J = 11.9 Hz), 3.92 (1 H, m), 3.80-3.48 (6 H, m), 2.90 (1.8 H, br s), 2.71 (1.2 H, m ), 2.67 (1 H, m), 2.25-2.01 (1 H, m), 1.92 - 1.72 (1 H, m), 1.67 (1 H, m), 1.24 (1 H, m). 13

[002605] C NMR (DMSOd6): 168.3, 167.7, 161.2, 161.2, 159.6, 159.5, 157.8, 157.8, 156.1, 156.1, 156, 155.9, 155.9, 131.4, 130.3, 130.2, 117.1, 115.7, 115.7, 115.6, 115.6, 114.3, 114.2, 112.9, 112.9, 112.8, 112.8, 69.3, 69.3, 69.3, 67.1, 67.1, 67.1, 67, 56.5, 52.9, 51.4, 29.9, 29.8, 29.7, 29.2, 29.2, 27.6, 26.4, 21.8, 21.7, 21.7, 21.7, 21, 2, 21.1.

[002606] Example 397: (R) -2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((tetrahydro-2H-pyran-4-yl) methyl) acetamide

[002607] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (2,3,5,6- tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a light cream powder.

[002608] 1H NMR (DMSOd6): 8.10 (1 H, br t, J = 5.7 Hz), 7.86 (1 H, m), 4.48 (1 H, quin, J = 8 , 5 Hz), 4.24 (1 H, dd, J = 11.5, 9.3 Hz), 3.82 (3 H, m), 3.44 (2 H, m), 3.40 ( 3 H, s), 3.31 (1 H, m), 3.22 (2 H, m), 2.95 (3 H, m), 1.62 (1 H, m), 1.51 ( 2 H, br d, J = 12.5 Hz), 1.12 (2 H, m). 13

[002609] C NMR (DMSOd6): 167.8, 156.2, 146.4, 146.4, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143, 7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.2, 120.4, 120.3, 120.2, 116.6, 105.9, 105.7, 105.6, 66.7, 49.4, 44.5, 34.9, 34.7, 31.5, 31.2, 30.4, 29.1.

[002610] Example 398: (R) -N-methyl-2- (2-methyl-6- (2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[002611] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (2,3,5,6- tetrafluorophenyl) - 3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002612] 1H NMR (DMSOd6): 7.86 (1 H, m), 5.24 (1 H, m), 4.72 (1.4 H, m), 4.65 (1.3 H , br t, J = 7.1 Hz), 4.59 (1.3 H, m), 4.48 (1 H, quin, J = 8.3 Hz), 4.24 (1 H, m) , 3.84 (1 H, m), 3.76, 3.73 (2 H, 2 s), 3.33 (3 H, s), 3.33 (1 H, m), 3.11 ( 1.8 H, s), 3.04 (1.2 H, s), 2.88 (1 H, m). 13

[002613] C NMR (DMSOd6): 168.6, 167.8, 156.3, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 143.7, 143.7, 143.7, 143.7, 143, 6, 143.6, 143.6, 143.6, 128.2, 128, 120.5, 120.4, 120.3, 116.3, 116.2, 105.9, 105.7, 105, 6, 74.6, 74.6, 74.2, 74.2, 51, 49.4, 49.2, 34.9, 31.5, 31.5, 30.7, 29.6, 29, 3, 29, 29, 27.9.

[002614] Example 399: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N - (((R) - tetrahydrofuran-3-yl) acetamide

[002615] The compound was prepared in an analogous manner to Example 34 from (S) -2- (2-methyl-6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5-acid, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white solid.

[002616] 1H NMR (DMSOd6): 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m), 5.09 (0.6 H, m), 4.65 (0.4 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, m), 3.92 (1 H, m ), 3.82 (2 H, m), 3.70 (2 H, m), 3.63 (1 H, m), 3.56 (1 H, m), 3.35 (3 H, 2 s), 3.26 (1 H, m), 2.94 (1.8 H, s), 2.86 (1 H, m), 2.74 (1.2 H, s), 2.21 (0.4 H, m), 2.09 (0.6 H, m), 1.86 (0.4 H, m), 1.76 (0.6 H, m). 13

[002617] C NMR (DMSOd6): 168.2, 167.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 156.2, 154.9, 154.9, 129.7, 129.6, 128.3, 128.1, 118.9, 118.8, 118.7, 116.5, 116.4, 116.1, 116, 1, 116, 115.9, 113.3, 113.2, 113.1, 113.1, 69.4, 69.2, 67.1, 67.1, 56.6, 53, 49.5, 34.8, 34.8, 31.5, 31.5, 30, 29.8, 29.7, 29.4, 29.3, 29.2, 27.6.

[002618] Example 400: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrole [1,2- c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[002619] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3 , 5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated like a beige solid.

[002620] 1H NMR (DMSOd6): 8.90 (1 H, d, J = 6.7 Hz), 7.64 (1 H, td, J = 8.7, 5.6 Hz), 7, 21 (1 H, m), 4.81 (1 H, m), 4.72 (2 H, m), 4.44 (2 H, td, J = 6.4, 1.5 Hz), 4 , 10 (1 H, d, J = 12.0 Hz), 3.80 (1 H, d, J = 12.2 Hz), 3.56 (2 H, m), 3.35 (3 H, s), 2.79 (1 H, dd, J = 8.4, 4.4 Hz), 1.69 (1 H, dd, J = 8.3, 5.5 Hz), 1.27 (1 H, t, J = 5.0 Hz). 13

[002621] C NMR (DMSOd6): 167.5, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.9, 156.2, 156.1, 130.8, 130.3, 130.2, 117, 116.9, 116.8, 116.1, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 77, 77, 52.2, 44.2, 31.5, 31, 25.6, 21.6, 21.2.

[002622] Example 401: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[002623] The compound was prepared analogously to Example 34 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white solid.

[002624] 1H NMR (DMSOd6): 11.75 (1 H, s), 7.96 (1 H, br d, J = 7.5 Hz), 7.61 (1 H, m), 7, 21 (1 H, t, J = 9.5 Hz), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.65 (3 H, m), 3.31 (1 H, m), 3.26 (2 H , s), 3.23 (1 H, dd, J = 9.4, 15.9 Hz), 3.08 (1 H, m), 2.84 (1 H, dd, J = 15.8, 8.1 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.45 (2 H, m). 13

[002625] C NMR (DMSOd6): 167.2, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 129, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114.3, 113.2, 113.2, 113, 1, 113.1, 70.2, 67, 48.5, 35.6, 31.4, 29.3, 28.6, 23.9.

[002626] Example 402: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[002627] The compound was prepared analogously to Example 34 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002628] 1H NMR (DMSOd6): 11.74 (1 H, s), 7.96 (1 H, br d, J = 7.6

Hz), 7.71 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.5, 9.2 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.65 (3 H, m), 3.34 (1H, m) , 3.25 (2 H, d, J = 2.9 Hz), 3.21 (1 H, dd, J = 16.0, 9.1 Hz), 3.09 (1 H, dd, J = 10.5, 7.8 Hz), 2.83 (1 H, dd, J = 15.7, 8.2 Hz), 1.79 (1 H, m), 1.65 (1 H, m) , 1.45 (2 H, m). 13

[002629] C NMR (DMSOd6): 167.2, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129, 118.8, 118.7, 118.6, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103, 9, 103.9, 70.2, 67, 48.6, 45.1, 35.6, 31.4, 29.4, 28.6, 23.9.

[002630] Example 403: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrole [1,2- c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[002631] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3 , 5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated like a beige solid.

[002632] 1H NMR (DMSOd6): 7.64 (1 H, td, J = 8.7, 5.6 Hz), 7.21 (1 H, m), 5.29 (1 H, m) , 4.76, 4.67, 4.60 (4 H, 3 m), 4.11 (1 H, m), 3.84 (3 H, m), 3.29 (3 H, 2 s) , 3.16 (1.8 H, m), 3.06 (1.2 H, s), 2.76 (0.6 H, dd, J = 8.3, 4.3 Hz), 2, 69 (0.4 H, dd, J = 8.4, 4.4 Hz), 1.68 (1 H, m), 1.25 (0.6 H, t, J = 5.0 Hz), 1.22 (0.4 H, t, J = 5.0 Hz). 13

[002633] C NMR (DMSOd6): 168.6, 167.8, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.9, 156.2, 156.1, 130.6, 130.3, 130.3, 130.2,

117, 117, 116.9, 116.8, 116.8, 116.3, 116.2, 115.8, 115.7, 115.6, 115.6, 112.9, 112.9, 112, 8, 112.8, 74.7, 74.6, 74.3, 74.2, 52.2, 52.2, 51.1, 49.1, 31.5, 31.5, 31.4, 30.7, 29.8, 29.4, 27.9, 25.7, 21.7, 21.2, 21.1.

[002634] Example 404: 2 - ((S) -6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[002635] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002636] 1H NMR (DMSOd6): 11.75 (1 H, s), 8.22 (1 H, br d, J = 6.6 Hz), 7.61 (1 H, td, J = 8 , 8, 5.6 Hz), 7.21 (1 H, t, J = 9.4 Hz), 4.44 (1 H, quin, J = 8.6 Hz), 4.21 (1 H, tt, J = 10.1, 3.8 Hz), 4.15 (1 H, dd, J = 11.5, 9.2 Hz), 3.73 (3 H, m), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 8.9, 3.7 Hz), 3.24 (2 H, s), 3.22 (1 H, dd, J = 6.3, 11.7 Hz), 2.84 (1 H, dd, J = 15.6, 8.1 Hz), 2.07 (1 H, m), 1 , 71 (1 H, m). 13

[002637] C NMR (DMSOd6): 167.5, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 129.1, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114.2, 113.3, 113.2, 113.1, 113.1, 72.4, 66.3, 49.8, 48.5, 35.6, 32, 31.3, 29.3.

[002638] Example 405: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[002639] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002640] 1H NMR (DMSOd6): 7.72 (1 H, td, J = 8.4, 5.8 Hz), 7.16 (1 H, br t, J = 9.4 Hz), 4 , 38 - 4.52 (1.6 H, m), 4.22 (1 H, m), 3.94 (0.4 H, m), 3.90 (2 H, m), 3.76 - 3.85 (1.8 H, m), 3.72 (1.2 H, s), 3.37 (2 H, m), 3.35 (3H, s), 3.28 (1H, m), 2.89 (1.8 H, s), 2.82 - 2.88 (1 H, m), 2.72 (1.2 H, s), 1.74 - 1.82 (0 , 8 H, m), 1.64 - 1.74 (1.2 H, m), 1.54 - 1.63 (0.8 H, m), 1.37 - 1.46 (1.2 H, m). 13

[002641] C NMR (DMSOd6): 167.7, 167.5, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 156.1, 155.9, 155.8, 132.5, 132.4, 128.2, 118.9, 118.8, 118.8, 118.7, 116.7, 116.5, 116.3, 113.8, 113, 6, 104.1, 103.9, 66.5, 66.3, 52.9, 49.7, 49.6, 34.8, 31.5, 31.5, 30.2, 30.2, 29.9, 29.5, 29.2, 29.1, 27.1.

[002642] Example 406: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002643] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002644] 1H NMR (DMSOd6): 8.11 (1 H, d, J = 7.6 Hz), 7.68 - 7.79 (1 H, m), 7.12 - 7.21 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.4, 9.3 Hz), 3.71 - 3.83 (4 H, m), 3.42 (2 H, d, J = 2.3 Hz), 3.40 (3 H, s), 3.33 (2H, m), 3.28 (1 H, dd, J = 15.9, 9.6 Hz), 2.88 (1 H, dd, J = 15.9, 8.0 Hz), 1.64 - 1.73 (2 H, m), 1 , 30 - 1.46 (2 H, m). 13

[002645] C NMR (DMSOd6): 166.8, 160.8, 160.7, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.4, 118.8, 118.7, 118.6, 116.4, 113.8, 113.6, 104.1, 104.1, 103.9, 103, 9, 65.8, 49.6, 45.2, 34.8, 32.4, 31.5, 31.3, 29.2.

[002646] Example 407: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole acid [1, 2-c] imidazol-1-yl) acetic

[002647] The compound was prepared analogously to Example 3 from (4S) -4- (3-chloro-2,6-difluorophenyl) -2- (3-ethoxy-3-oxopropanoyl) pyrrolidine-1-carboxylate tert-butyl and isolated as an off-white solid.

[002648] 1H NMR (DMSOd6): 12.56 (1 H, br s), 11.78 (1 H, s), 7.61 (1 H, td, J = 8.7, 5.6 Hz ), 7.21 (1 H, t, J = 8.9 Hz), 4.46 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.4 , 9.2 Hz), 3.74 (1 H, dd, J = 11.6, 7.9 Hz), 3.41 (2 H, s), 3.26 (1 H, dd, J = 9 , 3, 15.8 Hz), 2.87 (1 H, dd, J = 15.8, 8.2 Hz). 13

[002649] C NMR (DMSOd6): 170.7, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.3, 154.9, 154.9, 129.7, 129.7, 129.6, 118.8, 118.7, 118.6, 116.1, 116.1, 116, 115.9, 113.4, 113.3, 113.2, 113.1, 113.1, 48.6, 35.6, 29.9, 29.2.

[002650] Example 408: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[002651] The compound was prepared in an analogous manner to Example 32 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002652] 1H NMR (DMSOd6): 11.67 (1 H, br s), 7.72 (1 H, td, J = 8.4, 5.9 Hz), 7.18 (1 H, m ), 5.22 (1 H, m), 4.70 (1.33 H, m), 4.63 (1.3 H, m), 4.58 (1.3 H, m), 4, 44 (1 Hm), 4.15 (1 H, m), 3.69 (1 H, m), 3.51, 3.48

(2 H, m), 3.18 (1 H, m), 3.06, 3.02 (3 H, 2 s), 2.80 (1 H, m). 13

[002653] C NMR (DMSOd6): 168.6, 167.8, 160.8, 160.8, 159.2, 157.5, 157.5, 155.9, 155.8, 155.2, 155.1, 132.5, 132.4, 129.4, 129.3, 118.9, 118.7, 118.6, 114, 113.9, 113.8, 113.6, 104.1, 103.9, 74.6, 74.6, 74.2, 51, 49.1, 48.6, 35.7, 30.8, 29.7, 29.4, 29.3, 29.2, 28.

[002654] Example 409: (S) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole acid [ 1,2-c] imidazol-1-yl) acetic

[002655] The compound was prepared in a manner analogous to Example 229 from (4S) -2- (3-ethoxy-3-oxopropanoyl) -4- (2,3,6-trifluorophenyl) pyrrolidine-1-carboxylate tert-butyl and isolated as an off-white powder.

[002656] 1H NMR (DMSOd6): 12.73 (1 H, br s), 12.74 (1 H, m), 7.53 (1 H, m), 7.47 (1 H, m) , 7.18 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.24 (1 H, dd, J = 11.4, 9.2 Hz), 3 , 82 (1 H, dd, J = 11.6, 7.8 Hz), 3.65 (2 H, d, J = 0.7 Hz), 3.40 (3 H, s), 3.34 (1 H, m), 2.92 (1 H, dd, J = 15.9, 8.1 Hz). 13

[002657] C NMR (DMSOd6): 170.8, 156.9, 156.9, 156.4, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.6, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.7, 118.9, 118, 8, 118.8, 118.7, 116.5, 116.5, 116.4, 116.3, 115.6, 112, 112, 112, 111.9, 111.8, 111.8, 111, 8, 111.8, 49.5, 34.7, 31.4, 29.8, 29.1.

[002658] Example 410: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002659] The compound was prepared in an analogous manner to Example 32 from (R) -2- (3-thioxo-6- (3-bromo-2,6-difluorophenyl) -2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002660] 1H NMR (DMSOd6): 11.75 (1 H, s), 7.97 (1 H, d, J = 7.5 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.2 Hz), 3.80 (2 H, dt, J = 11.4, 3.6 Hz), 3.72 (2 H, m), 3.31 (2 H, m), 3.24 (2 H, s), 3.23 ( 1 H, dd, J = 9.4, 16 Hz), 2.83 (1 H, dd, J = 15.9, 8.1 Hz), 1.67 (2 H, m), 1.37 ( 2 H, m). 13

[002661] C NMR (DMSOd6): 166.8, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129, 118.8, 118.7, 118.6, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103, 9, 103.9, 65.8, 48.6, 45.2, 35.6, 32.4, 31.5, 29.4.

[002662] Example 411: (S) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -1-morpholinoetan-1-one

[002663] The compound was prepared analogously to Example 32 from (S) -2- (6- (2,3,6-trifluorophenyl) -2-methyl-3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002664] 1H NMR (DMSOd6): 7.47 (1 H, qd, J = 9.4, 5.1 Hz), 7.18 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.24 (1 H, m), 3.81 (1 H, dd, J = 11.4, 7.9 Hz), 3.75 (2 H, s), 3 , 59 (2 H, m), 3.55 (2 H, m), 3.49 (2 H, m), 3.45 (2 H, m), 3.36 (3 H, s), 3 , 28 (1 H, dd, J = 15.8, 9.3 Hz), 2.88 (1 H, dd, J = 15.8, 8.1 Hz).

[002665] 13C NMR (DMSOd6): 166.8, 157, 157, 156.9, 156.9, 156.3, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128, 2, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.3, 112, 112, 112, 111.9, 111, 8, 111.8, 111.8, 111.8, 66, 66, 49.4, 45.6, 41.7, 34.8, 31.5, 29.2, 28.8.

[002666] Example 412: 2 - ((S) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002667] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002668] 1H NMR (DMSOd6): 8.37 (1 H, br d, J = 6.5 Hz), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7 , 18 (1 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4.23 (2 H, m), 3.81 (1 H, dd, J = 11.0 , 7.6 Hz), 3.78 (1 H, q, J = 7.1 Hz), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, dd, J = 9.0, 3.5 Hz), 3.43 (2 H, m), 3.40 (3 H, s), 3.29 (1 H, br dd, J = 15.7, 9.2 Hz), 2.90 (1 H, dd, J = 15.8, 8.2 Hz), 2.08 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m). 13

[002669] C NMR (DMSOd6): 167.6, 157, 156.9, 156.2, 155.3, 155.3, 149.1, 149, 149, 149, 147.6, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.4, 118.9, 118.8, 118.7, 118.6, 116, 5, 116.5, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 72.4, 66.3, 49, 8, 49.4, 34.7, 32, 31.5, 31.1, 29.1.

[002670] Example 413: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[002671] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002672] 1H NMR (DMSOd6): 8.84 (1 H, br d, J = 6.6 Hz), 7.72 (1 H, m), 7.18 (1 H, m), 4, 78 (1 H, m), 4.70 (2 H, td, J = 6.9, 2.2 Hz), 4.42 (3 H, m), 4.22 (1 H, dd, J = 11.4, 9.2 Hz), 3.79 (1 H, dd, J = 11.6, 7.8 Hz), 3.47 (2 H, m), 3.39 (3 H, s) , 3.28 (1 H, dd, J = 15.8, 9.3 Hz), 2.89 (1 H, dd, J = 15.8, 8.1 Hz). 13

[002673] C NMR (DMSOd6): 167.5, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.3, 155.9, 155.9, 132.5, 132.4, 128.7, 118.8, 118.6, 118.5, 116, 113.8, 113.6, 104.1, 104.1, 103.9, 103.9, 77, 77, 49.6, 44.2, 34.8, 31.5, 31, 29.2.

[002674] Example 414: (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[002675] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002676] 1H NMR (DMSOd6): 8.85 (1 H, br d, J = 6.6 Hz), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7 , 19 (1 H, m), 4.78 (1 H, m), 4.70 (2 H, m), 4.41 (3 H, t, J = 6.3 Hz), 4.23 ( 1 H, m), 3.81 (1 H, dd, J = 11.5, 8.0 Hz), 3.48 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.3 Hz), 2.91 (1 H, dd, J = 15.8, 8.4 Hz). 13

[002677] C NMR (DMSOd6): 167.5, 157, 156.9, 156.3, 155.4, 155.3, 149.1, 149.1, 149, 149, 147.6, 147, 5, 147.5, 147.4, 147.4, 147.4, 147.3, 146, 145.9, 145.9, 145.8, 128.6, 118.8, 118.7, 118, 7, 118.6, 116.5, 116.5, 116.4, 116.3, 116.1, 112, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 77, 77, 49.5, 44.2, 34.7, 31.5, 31, 29.1.

[002678] Example 415: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[002679] The compound was prepared analogously to Example 34 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2 acid, 3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a beige solid.

[002680] 1H NMR (DMSOd6): 8.17 (1 H, br d, J = 7.3 Hz), 7.64 (1 H, td, J = 8.7, 5.7 Hz), 7 , 21 (1 H, m), 4.10 (1 H, d, J = 12.2 Hz), 3.80 (1 H, d, J = 12.0 Hz), 3.68 (3 H, m), 3.53 (2 H, m), 3.39 (1 H, m), 3.35 (3 H, s), 3.14 (1 H, m), 2.78 (1 H, dd, J = 8.4, 4.4 Hz), 1.83 (1 H, m), 1.69 (2 H, m), 1.48 (2 H, m), 1.25 (1 H , t, J = 5.0 Hz). 13

[002681] C NMR (DMSOd6): 167.4, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.8, 156.2, 156.1, 130.6, 130.3, 130.2, 117.1, 116.9, 116.8, 116.5, 115.7, 115.7, 115.6, 115.6, 112.9, 112, 9, 112.8, 112.8, 70.1, 67, 52.2, 45.1, 31.4, 31.1, 28.6, 25.6, 23.9, 21.7, 21, two.

[002682] Example 416: (S) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002683] The compound was prepared analogously to Example 32 from (S) -2- (6- (2,3,6-trifluorophenyl) -2-methyl-3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a light beige powder.

[002684] 1H NMR (DMSOd6): 8.11 (1 H, d, J = 7.5 Hz), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7, 18 (1 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 11.4, 9.4 Hz), 3.81 ( 3 H, m), 3.75 (1 H, m), 3.42 (2 H, m), 3.40 (3 H, s), 3.33 (2 H, m), 3.29 ( 1 H, dd, J = 15.8, 9.2 Hz), 2.90 (1 H, dd, J = 15.8, 8.3 Hz), 1.69 (2 H, m), 1, 38 (2 H, m).

[002685] C NMR (DMSOd6): 166.8, 157, 156.9, 156.2, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148, 9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.9, 145.8, 128.3, 118.9, 118.8, 118.8, 118.7, 116.5, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 65.8, 49.4, 45.2, 34.7, 32.4, 31.5, 31.3, 29.2.

[002686] Example 417: 2 - ((S) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[002687] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002688] 1H NMR (DMSOd6): 8.37 (1 H, d, J = 6.6 Hz), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7, 16 (1 H, t, J = 9.6 Hz), 4.43 (1 H, quin, J = 8.6 Hz), 4.23 (2 H, m), 3.77 (3 H, m ), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, br dd, J = 9.0, 3.6 Hz), 3.43 (2 H, s), 3.40 (3 H, m), 3.29 (1 H, dd, J = 15.8, 9.2 Hz), 2.90 (1 H, dd, J = 15.8 , 8.2 Hz), 2.08 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m). 13

[002689] C NMR (DMSOd6): 167.6, 157, 156.9, 156.9, 156.2, 155.3, 155.3, 155.3, 149.1, 149, 149, 148, 9, 147.5, 147.5, 147.5, 147.4,

147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.4, 118.9, 118.8, 118.8, 118.7, 116, 5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 72.4, 66.3, 49, 8, 49.4, 34.7, 32, 31.5, 31.1, 29.1.

[002690] Example 418: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[002691] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3 , 5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated like a gray solid.

[002692] 1H NMR (DMSOd6): 8.41 (1 H, d, J = 6.7 Hz), 7.64 (1 H, td, J = 8.7, 5.7 Hz), 7, 21 (1 H, td, J = 9.1, 1.2 Hz), 4.25 (1 H, m), 4.10 (1 H, d, J = 12.0 Hz), 3.80 ( 2 H, m), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3, 52 (2 H, m), 3.48 (1 H, dd, J = 8.9, 3.6 Hz), 3.36 (3 H, s), 2.79 (1 H, dd, J = 8.4, 4.4 Hz), 2.09 (1 H, dq, J = 12.7, 7.6 Hz), 1.74 (1 H, m), 1.69 (1 H, dd, J = 8.4, 5.6 Hz), 1.26 (1 H, t, J = 5.0 Hz). 13

[002693] C NMR (DMSOd6): 167.6, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.8, 156.2, 156.1, 130.6, 130.3, 130.2, 117.1, 116.9, 116.8, 116.5, 115.7, 115.7, 115.6, 115.6, 112.9, 112, 9, 112.8, 112.8, 72.4, 66.3, 52.2, 49.8, 32, 31.5, 31, 25.6, 21.7, 21.2.

[002694] Example 419: (S) -2- (6- (3,5-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-morpholinoetan-1-one

[002695] The compound was prepared analogously to Example 32 from (S) -2- (6- (3,5-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetra -hydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002696] 1H NMR (DMSOd6): 7.13 (3 H, m), 4.23 (1 H, dd, J = 11.2, 7.8 Hz), 4.07 (1 H, quin, J = 8.0 Hz), 3.76 (3 H, m), 3.60 (2 H, br t, J = 4.3 Hz), 3.56 (2 H, br d, J = 4, 0 Hz), 3.51 (2 H, m), 3.45 (2 H, m), 3.36 (3 H, s), 3.20 (1 H, dd, J = 15.3, 7 , 9 Hz), 2.84 (1 H, dd, J = 15.3, 8.4 Hz). 13

[002697] C NMR (DMSOd6): 166.8, 163.3, 163.2, 161.7, 161.6, 156.4, 145.8, 145.7, 145.7, 128.4, 116.6, 110.7, 110.7, 110.6, 110.6, 102.7, 102.5, 102.3, 66, 51, 45.6, 45.5, 41.7, 31, 5, 30.4, 28.7.

[002698] Example 420: (R) -N-methyl-N- (oxetan-3-yl) -2- (3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide

[002699] The compound was prepared in an analogous manner to Example 32 from (R) -2- (6- (2,3,6-trifluorophenyl) -2-methyl-3-thioxo-2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002700] 1H NMR (DMSOd6): 11.68 (1 H, br s), 7.47 (1 H, m), 7.17 (1 H, m), 5.22 (1 H, m) , 4.70 (1.33 H, m), 4.63 (1.33 H, m), 4.58 (1.33 H, m), 4.43 (1 H, m), 4.16 (1 H, m), 3.74 (1 H, m), 3.52, 3.49 (2 H, 2s), 3.19 (1 H, m), 3.05, 3.01 (3 H, 2 s), 2.82 (1 H, m). 13

[002701] C NMR (DMSOd6): 168.6, 167.8, 157, 155.3, 155.3, 155.2, 155.2, 149.1, 147.5, 147.5, 129, 3, 129.2, 118.8, 116.5, 116.4, 116.4, 116.3, 114.1, 114, 112, 111.8, 74.6, 74.6, 74.2, 51, 49.1, 48.5, 35.6, 30.8, 29.7, 29.4, 29.2, 29.1, 28.

[002702] Example 421: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrole [1,2- c] imidazol-1-yl) -1-morpholinoetan-1-one

[002703] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3 , 5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated like a whitish powder.

[002704] 1H NMR (DMSOd6): 7.64 (1 H, td, J = 8.7, 5.7 Hz), 7.21 (1 H, m), 4.11 (1 H, d, J = 12.2 Hz), 3.83 (2 H, m), 3.80 (1 H, d, J = 12.2 Hz), 3.62 (2 H, m), 3.57 (2 H, m), 3.52 (2 H, m), 3.47 (2 H, m), 3.33 (3 H, s), 2.75 (1 H, dd, J = 8.4, 4.4 Hz), 1.71 (1 H, dd, J = 8.3, 5.5 Hz), 1.26

(1 H, t, J = 5.0 Hz). 13

[002705] C NMR (DMSOd6): 166.8, 161.2, 161.2, 159.6, 159.6, 157.8, 157.8, 156.9, 156.1, 156.1, 130.4, 130.3, 130.2, 117, 116.9, 116.8, 116.2, 115.7, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.7, 66, 52.2, 45.7, 41.7, 31.5, 29, 25.7, 21.8, 21.2.

[002706] Example 422: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -1-morpholinoetan-1-one

[002707] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002708] 1H NMR (DMSOd6): 7.45 (2 H, m), 7.30 (1 H, dd, J = 10.0, 8.8 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12 Hz), 3.82 (2 H, m), 3.62 (2 H, m), 3.58 (2 H, br t, J = 4.8 Hz), 3.53 (2 H, m), 3.47 (2 H, m), 3.33 (3 H, s), 2.86 (1 H, dd, J = 8.3, 4.2 Hz), 1.72 (1 H, dd, J = 8.3, 5.4 Hz), 1.13 (1 H, t, J = 4.8 Hz). 13

[002709] C NMR (DMSOd6): 166.8, 161.3, 159.6, 156.9, 130.7, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.2, 117.6, 117.4, 115.9, 66, 52.4, 52.4, 45.7, 41.7, 31.6, 31.5, 28.9, 22.1, 20.7.

[002710] Example 423: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002711] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3 , 5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated like a light gray solid.

[002712] 1H NMR (DMSOd6): 8.16 (1 H, d, J = 7.6 Hz), 7.64 (1 H, td, J = 8.7, 5.6 Hz), 7, 22 (1 H, m), 4.10 (1 H, d, J = 12.0 Hz), 3.80 (4 H, m), 3.50 (2 H, m), 3.36 (3 H, s), 3.34 (2 H, m), 2.79 (1 H, dd, J = 8.4, 4.4 Hz), 1.71 (3 H, m), 1.41 ( 2 H, m), 1.26 (1 H, t, J = 5.0 Hz). 13

[002713] C NMR (DMSOd6): 166.9, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.8, 156.2, 156.1, 130.6, 130.3, 130.2, 117.1, 116.9, 116.8, 116.6, 115.7, 115.7, 115.6, 115.6, 112.9, 112, 9, 112.8, 112.8, 65.8, 52.2, 45.2, 32.4, 32.3, 31.4, 31.3, 25.6, 21.7, 21.3.

[002714] Example 424: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H- acid pyrrole [1,2-c] imidazol-1-yl) acetic

[002715] The compound was prepared in a manner analogous to

Example 229 from tert-butyl (4S) -2- (3-ethoxy-3-oxopropanoyl) -4- (3-chloro-2,6-difluorophenyl) pyrrolidine-1-carboxylate and isolated as an off-white solid.

[002716] 1H NMR (DMSOd6): 12.73 (1 H, s), 7.62 (1 H, td, J = 8.8, 5.6 Hz), 7.22 (1 H, m) , 4.46 (1 H, m), 4.24 (1 H, dd, J = 11.6, 9.2 Hz), 3.81 (1 H, dd, J = 11.6, 7.6 Hz), 3.65 (2 H, m), 3.40 (3 H, s), 3.33 (1 H, dd, J = 9.3, 15.9 Hz), 2.91 (1 H , dd, J = 16.1, 8.1 Hz). 13

[002717] C NMR (DMSOd6): 170.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.4, 154.9, 154.9, 129.7, 129.7, 128.7, 118.8, 118.7, 118.6, 116.1, 116, 116, 115.9, 115.5, 113.3, 113.2, 113, 1, 113.1, 49.6, 34.7, 31.4, 29.8, 29.1.

[002718] Example 425: 2 - ((S) -6- (3,5-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002719] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (3,5- difluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002720] 1H NMR (DMSOd6): 8.37 (1 H, br d, J = 6.6 Hz), 7.13 (3 H, m), 4.23 (2 H, m), 4, 07 (1 H, quin, J = 8.0 Hz), 3.76 (3 H, m), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3.46 ( 3 H, m), 3.40 (3 H, s), 3.23 (1 H, dd, J = 15.4, 7.9 Hz), 2.86 (1 H, dd, J = 15, 4, 8.4 Hz), 2.08 (1 H, m), 1.72 (1 H, m).

[002721] C NMR (DMSOd6): 167.6, 163.3, 163.2, 161.7, 161.6, 156.4, 145.8, 145.8, 145.7, 128.5, 116.6, 110.7, 110.7, 110.6, 110.5, 102.6, 102.5, 102.3, 72.4, 66.3, 51.1, 49.8, 45, 4, 32, 31.5, 31, 30.4.

[002722] Example 426: 2 - ((S) -6- (3,5-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((S) -tetrahydrofuran-3-yl) acetamide

[002723] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (3,5- difluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002724] 1H NMR (DMSOd6): 8.37 (1 H, br d, J = 6.6 Hz), 7.13 (3 H, m), 4.23 (2 H, m), 4, 07 (1 H, quin, J = 8.0 Hz), 3.75 (3 H, m), 3.67 (1 H, td, J = 8.3, 5.5 Hz), 3.48 ( 1 H, br d, J = 3.5 Hz), 3.45 (2 H, s), 3.40 (3 H, s), 3.23 (1 H, dd, J = 15.4, 7 , 9 Hz), 2.86 (1 H, dd, J = 15.3, 8.3 Hz), 2.08 (1 H, m), 1.72 (1 H, m). 13

[002725] C NMR (DMSOd6): 167.6, 163.3, 163.2, 161.7, 161.6, 156.4, 145.9, 145.8, 145.7, 128.5, 116.6, 110.7, 110.7, 110.6, 110.5, 102.6, 102.5, 102.3, 72.4, 66.3, 51.1, 49.8, 45, 4, 32, 31.5, 31, 30.4.

[002726] Example 427 (S) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1, 2-c] imidazol-1-yl) -N - (((tetrahydro-2H-pyran-4-yl) methyl) acetamide

[002727] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (2,3,6-trifluorophenyl) -3- thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002728] 1H NMR (DMSOd6): 8.10 (1 H, br t, J = 5.8 Hz), 7.47 (1 H, qd, J = 9.5, 4.9 Hz), 7 , 18 (1 H, m), 4.43 (1 H, quin, J = 8.7 Hz), 4.23 (1 H, dd, J = 11.3, 9.4 Hz), 3.81 (3 H, m), 3.44 (2 H, m), 3.40 (3 H, s), 3.29 (1 H, dd, J = 15.9, 9.2 Hz), 3, 22 (2 H, tt, J = 11.7, 2.3 Hz), 2.96 (2 H, m), 2.90 (1 H, dd, J = 15.8, 8.3 Hz), 1.62 (1 H, m), 1.51 (2 H, m), 1.13 (2 H, m). 13

[002729] C NMR (DMSOd6): 167.8, 157, 156.9, 156.2, 155.3, 155.3, 149.1, 149, 149, 149, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.9, 145.8, 128.4, 118.9, 118, 8, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111, 8, 66.7, 49.4, 44.5, 34.7, 34.7, 31.5, 31.2, 30.4, 29.2.

[002730] Example 428: (S) -2- (6- (3,5-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - (((tetrahydro-2H-pyran-4-yl) methyl) acetamide

[002731] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (3,5-difluorophenyl) -3 - thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002732] 1H NMR (DMSOd6): 8.10 (1 H, t, J = 5.8 Hz), 7.13 (3 H, m), 4.23 (1 H, dd, J = 11, 2, 7.9 Hz), 4.07 (1 H, quin, J = 8.0 Hz), 3.82 (2 H, m), 3.75 (1 H, dd, J = 11.2, 7.8 Hz), 3.46 (2 H, m), 3.40 (3 H, s), 3.22 (3 H, m), 2.97 (2 H, m), 2.85 ( 1 H, dd, J = 15.4, 8.2 Hz), 1.63 (1 H, m), 1.51 (2 H, m), 1.14 (2 H, m). 13

[002733] C NMR (DMSOd6): 167.8, 163.3, 163.2, 161.7, 161.6, 156.4, 145.9, 145.9, 145.8, 128.6, 116.7, 110.7, 110.7, 110.6, 110.6, 102.7, 102.5, 102.3, 66.7, 51.2, 45.4, 44.5, 34, 8, 31.4, 31.1, 30.4, 30.4.

[002734] Example 429: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[002735] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (3-chloro-2,6- difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002736] 1H NMR (DMSOd6): 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m), 5.24 (1 H, m) , 4.72, 4.64, 4.59 (4 H, m), 4.43 (1 H, m), 4.23 (1 H, m), 3.80 (1 H, m), 3 , 75, 3.72 (2 H, m), 3.33 (3H, s), 3.24 (1 H, m), 3.11 (1.8 H, s), 3.03 (1, 2 H, s), 2.83 (1 H, m). 13

[002737] C NMR (DMSOd6): 168.6, 167.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 128.1, 118.9, 118.8, 118.6, 116.3, 116.1, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 74.6, 74.6, 74.2, 74.2, 51, 49.5, 49.2, 34.8, 31.5, 31.5, 30.7, 29.6, 29.3, 29.1, 29.1, 27.9.

[002738] Example 430: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N - (((1-methyl-1H-pyrazol-4-yl) methyl) acetamide

[002739] The compound was prepared analogously to Example 168 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7-tetra -hydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) acetic acid and isolated as an off-white solid.

[002740] 1H NMR (DMSOd6): 7.70 (0.4 H, s), 7.62 (1 H, td, J = 8.7, 5.6 Hz), 7.59 (0.6 H, s), 7.41 (0.4 H, s), 7.31 (0.6 H, s), 7.22 (1 H, m), 4.42 (1.8 H, m) , 4.32 (0.6 H, m), 4.27 (0.6 H, m), 4.21 (1 H, m), 3.80 (3

H, m), 3.71 (3 H, m), 3.36 (3 H, 2 s), 3.21 (1 H, m), 2.97 (1.8 H, s), 2, 81 (1.2 H, s), 2.80 (1 H, m). 13

[002741] C NMR (DMSOd6): 167.6, 167.5, 160.1, 160.1, 158.5, 158.5, 156.6, 156.6, 156.5, 156.5, 156.2, 154.9, 154.9, 154.9, 154.9, 138.4, 137.8, 129.9, 129.7, 129.6, 129.5, 128.2, 128, 2, 118.8, 118.8, 118.7, 118.6, 118.6, 116.7, 116.6, 116.5, 116.4, 116.1, 116, 115.9, 115, 9, 113.3, 113.2, 113.1, 113.1, 49.5, 43.6, 41, 38.5, 38.3, 34.7, 34.7, 34.6, 33, 31.5, 31.5, 29.4, 29.1, 29.1, 29.

[002742] Example 431: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[002743] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002744] 1H NMR (DMSOd6): 7.45 (2 H, m), 7.30 (1 H, dd, J = 10.1, 8.7 Hz), 5.29 (1 H, m) , 4.77, 4.74, 4.66, 4.61 (4 H, 4 m), 4.15 (1 H, m), 3.83 (3 H, m), 3.30 (3 H , 2 s), 3.16 (1.8 H, s), 3.06 (1.2 H, s), 2.87 (0.6 H, dd, J = 8.4, 4.3 Hz ), 2.79 (0.4 H, dd, J = 8.3, 4.2 Hz), 1.69 (1 H, m), 1.12 (0.6 H, t, J = 4, 8 Hz), 1.09 (0.4 H, m). 13

[002745] C NMR (DMSOd6): 168.6, 167.8, 161.3, 159.6, 156.9, 130.9, 130.6, 130.3, 130.2, 130.2, 129.4, 129.3, 128.7, 128.7, 128.6,

128.6, 128.3, 128.3, 117.6, 117.4, 116, 115.8, 74.7, 74.6, 74.3, 74.2, 52.4, 51.1, 49.1, 31.6, 31.5, 31.5, 30.7, 29.7, 29.4, 27.9, 22.1, 22, 20.7, 20.6.

[002746] Example 432: (S) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrole [1 , 2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[002747] The compound was prepared in an analogous manner to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,3, 6- trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white powder.

[002748] 1H NMR (DMSOd6): 8.85 (1 H, d, J = 6.6 Hz), 7.47 (1 H, qd, J = 9.5, 5.0 Hz), 7, 18 (1 H, m), 4.79 (1 H, m), 4.70 (2 H, m), 4.41 (3 H, m), 4.23 (1 H, dd, J = 11 , 4, 9.2 Hz), 3.81 (1 H, dd, J = 11.6, 7.9 Hz), 3.48 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.2 Hz), 2.91 (1 H, dd, J = 15.8, 8.3 Hz). 13

[002749] C NMR (DMSOd6): 167.5, 157, 156.9, 156.3, 155.4, 155.3, 149.1, 149, 149, 149, 147.6, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.6, 118.8, 118.7, 118, 7, 118.6, 116.5, 116.5, 116.4, 116.3, 116, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 77, 77, 49.5, 44.2, 34.7, 31.5, 31, 29.1.

[002750] Example 433: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[002751] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002752] 1H NMR (DMSOd6): 8.87 (1 H, d, J = 6.6 Hz), 7.47 (1 H, dd, J = 6.5, 2.7 Hz), 7, 43 (1 H, ddd, J = 8.8, 4.4, 2.7 Hz), 7.30 (1 H, dd, J = 10.1, 8.8 Hz), 4.82 (1 H , m), 4.72 (2 H, dd, J = 7.4, 6.1 Hz), 4.44 (2 H, td, J = 6.3, 2.6 Hz), 4.15 ( 1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.55 (2 H, m), 3.34 (3 H, s), 2.90 (1 H, dd, J = 8.4, 4.0 Hz), 1.69 (1 H, dd, J = 8.4, 5.3 Hz), 1.15 (1 H, t , J = 4.8 Hz). 13

[002753] C NMR (DMSOd6): 167.5, 161.3, 159.6, 156.9, 131.2, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 115.7, 77, 77, 52.4, 52.4, 44.2, 31.6, 31.5, 30, 9, 22, 20.7.

[002754] Example 434: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[002755] The compound was prepared in an analogous manner to Example 32 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002756] 1H NMR (DMSOd6): 7.44 (2 H, m), 7.30 (1 H, m), 4.49 (0.6 H, m), 4.15 (1 H, br d, J = 12.0 Hz), 4.01 (0.4 H, m), 3.85 (3 H, m), 3.80 (1 H, m), 3.41 (3 H, m ), 3.31 (3 H, m), 2.93 (2.2 H, m), 2.87 (0.6 H, dd, J = 8.4, 4.3 Hz), 2.74 (1.2 H, s), 1.87-1.59 (3.8 H, m), 1.43 (1.2 H, m), 1.13 (1 H, m). 13

[002757] C NMR (DMSOd6): 167.7, 167.6, 161.3, 159.6, 156.9, 156.8, 130.8, 130.7, 130.2, 130.2, 130.2, 129.4, 129.3, 128.8, 128.6, 128.3, 128.3, 117.6, 117.4, 116.4, 116.2, 66.5, 66, 3, 53, 52.4, 49.8, 31.7, 31.6, 31.5, 31.5, 30.2, 30, 29.6, 29.3, 29.2, 29.1, 27.1, 22.2, 22.1, 20.7, 20.7.

[002758] Example 435: (S) -N-methyl-2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H -pyrrole [1,2-c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[002759] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (2,3,6-trifluorophenyl) -3- thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a yellowish powder.

[002760] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.17 (1 H, m), 5.24 (1 H, m), 4.73, 4.64, 4, 59 (4 H, m), 4.42 (1 H, m), 4.24 (1 H, m), 3.81 (1 H, m), 3.73 (2 H, m), 3, 33 (3 H, 2 s), 3.25 (1H, m), 3.11 (1.8 H, s), 3.03 (1.2 H, s), 2.87 (1 H, m ). 13

[002761] C NMR (DMSOd6): 168.6, 167.8, 157, 156.9, 156.9, 156.3, 155.3, 155.3, 149.2, 149.1, 149, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 128.4, 128, 1, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.2, 112, 112, 112, 111.8, 111, 8, 111.8, 111.8, 74.6, 74.6, 74.2, 74.2, 51, 49.4, 49.2, 34.7, 34.7, 31.5, 31, 5, 31.4, 30.7, 29.9, 29.6, 29.3, 29.1, 29.1, 27.9.

[002762] Example 436: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -1-morpholinoetan-1-one

[002763] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a persimmon solid.

[002764] 1H NMR (DMSOd6): 7.57 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12.1 Hz), 3.82 (2 H, m), 3.64 (2 H, m), 3.58 (2 H, m), 3.53 (2 H, m), 3.47 (2 H, m), 3.33 (3 H, 2 s), 2.86 (1 H, dd, J = 8.4 , 4.3 Hz), 1.71 (1 H, dd, J = 8.3, 5.4 Hz), 1.13 (1 H, t, J = 4.8 Hz). 13

[002765] C NMR (DMSOd6): 166.9, 161.8, 160.2, 156.9, 133.1, 133.1, 132.4, 132.3, 130.7, 129.1, 129, 118, 117.9, 116.2, 116.2, 115.9, 66, 52.4, 45.7, 41.7, 31.6, 31.5, 28.9, 22.1, 20.7.

[002766] Example 437: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3.4] pyrrolo [1,2- c] imidazol-1-yl) -N- (oxetan-3-yl) acetamide

[002767] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a gray solid.

[002768] 1H NMR (DMSOd6): 8.87 (1 H, d, J = 6.7 Hz), 7.59 (1 H, dd, J = 6.7, 2.6 Hz), 7, 56 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.82 (1 H , m), 4.72 (2 H, t, J = 6.8 Hz), 4.44 (2 H, td, J = 6.4, 2.3 Hz), 4.14 (1 H, d , J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.55 (2 H, m), 3.34 (3 H, br s), 2.90 (1 H, dd, J = 8.4, 4.1 Hz), 1.69 (1 H, dd, J = 8.4, 5.4 Hz), 1.15 (1 H, t, J = 4.8 Hz). 13

[002769] C NMR (DMSOd6): 167.6, 161.8, 160.1, 156.9, 133.1, 133, 132.4, 132.3, 131.2, 129.2, 129, 1, 118, 117.9, 116.2, 116.2, 115.7, 77, 77, 52.5, 52.4, 44.2, 31.5, 31.5, 30.9, 22, 20.7.

[002770] Example 438: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[002771] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002772] 1H NMR (DMSOd6): 7.56 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 5.29 (1 H, m) , 4.75, 4.66, 4.62 (4 H, 4 m), 4.14 (1 H, m), 3.83 (3

H, m), 3.29 (3 H, 2 s), 3.15 (1.8 H, s), 3.06 (1.2 H, s), 2.87 (0.6 H, dd , J = 8.3, 4.2 Hz), 2.79 (0.4 H, dd, J = 8.3, 4.2 Hz), 1.69 (1 H, m), 1.12 ( 0.6 H, t, J = 4.8 Hz), 1.08 (0.4 H, m). 13

[002773] C NMR (DMSOd6): 168.6, 167.8, 161.8, 160.2, 156.9, 133.1, 133.1, 133, 132.4, 132.3, 130, 9, 130.6, 129.2, 129.1, 129.1, 129, 118, 117.8, 116.2, 116.2, 116, 115.8, 74.7, 74.6, 74, 3, 74.2, 52.4, 51.1, 49.1, 31.6, 31.5, 31.5, 30.7, 29.7, 29.3, 27.9, 22.1, 22, 20.6, 20.6.

[002774] Example 439: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[002775] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a light beige solid.

[002776] 1H NMR (DMSOd6): 77.57 (2 H, m), 7.24 (1 H, m), 4.49 (0.6 H, m), 4.15 (1 H, br d, J = 11.6 Hz), 4.01 (0.4 H, m), 3.97-3.73 (5 H, m), 3.51-3.24 (5 H, m), 2.93 (2.2 H, m), 2.87 (0.6 H, dd, J = 8.3, 4.2 Hz), 2.74 (1.2 H, s), 1.88 -1.58 (3.8 H, m), 1.45 (1.2 H, m), 1.12 (1 H, m). 13

[002777] C NMR (DMSOd6): 167.7, 167.6, 161.8, 160.1, 156.9, 156.8, 133, 132.4, 132.3, 130.7, 130, 7, 129.2, 129.1, 118, 117.8, 116.4, 116.2, 116.2, 66.5, 66.3, 52.9, 52.4, 49.7, 31, 6, 31.5, 31.5, 31.5, 30.2, 30.2, 30, 29.6, 29.3, 29.2, 29.1, 27.1, 22.2, 22, 1, 20.7, 20.6.

[002778] Example 440: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[002779] The compound was prepared analogously to Example 34 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3 acid, 5.5a, 6.6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a light yellow solid.

[002780] 1H NMR (DMSOd6): 7.58 (2 H, m), 7.25 (1 H, dd, J = 10.1, 8.9 Hz), 5.13 (0.6 H, m), 4.73 (0.4 H, m), 4.16 (1 H, d, J = 11.9 Hz), 4.0 - 3.51 (7 H, m), 3.32 ( 3 H, 2 s), 2.98 (1.8 H, s), 2.87 (1 H, m), 2.77 (1.2 H, s), 2.26 (0.4 H, m), 2.15 (0.6 H, m), 1.91 (0.4 H, m), 1.81 (0.6 H, m), 1.70 (1 H, m), 1 , 13 (1 H, m). 13

[002781] C NMR (DMSOd6): 168.3, 167.7, 167.6, 161.8, 161.8, 160.2, 160.1, 156.9, 156.8, 133.1, 133, 132.4, 132.3, 130.8, 130.7, 130.6, 129.2, 129.1, 129.1, 129, 118, 117.8, 116.2, 116.2, 116.1, 69.4, 69.3, 67.1, 67.1, 67, 53, 52.4, 31.6, 31.6, 31.5, 31.5, 31.3, 29, 9, 29.9, 29.8, 29.4, 29.3, 27.7, 22.1, 21.6, 20.7.

[002782] Example 441: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[002783] The compound was prepared analogously to Example 34 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3 acid, 5.5a, 6.6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a beige solid.

[002784] 1H NMR (DMSOd6): 7.45 (2 H, m), 7.30 (1 H, m), 5.13 (0.6 H, m), 4.73 (0.4 H , m), 4.15 (1 H, br d, J = 11.9 Hz), 4.0-3.52 (7 H, m), 3.31 (3 H, 2 s), 2.97 (1.8 H, s), 2.86 (1 H, m), 2.76 (1.2 H, s), 2.26 (0.4 H, m), 2.13 (0.6 H, m), 1.91 (0.4 H, m), 1.80 (0.6 H, m), 1.69 (1 H, m), 1.13 (1 H, m). 13

[002785] C NMR (DMSOd6): 168.3, 167.7, 161.3, 161.3, 159.7, 159.6, 156.9, 156.8, 130.8, 130.7, 130.6, 130.2, 129.4, 129.3, 128.8, 128.7, 128.7, 128.6, 128.3, 117.6, 117.4, 116.2, 116, 1, 69.4, 69.4, 69.3, 67.1, 67.1, 56.6, 53, 52.4, 31.6, 31.5, 31.5, 29.9, 29, 9, 29.8, 29.8, 29.4, 29.3, 27.7, 22.1, 20.7, 20.7.

[002786] Example 442: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrole [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydrofuran-3-yl) acetamide

[002787] The compound was prepared analogously to Example 34 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2 acid, 3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a light beige solid.

[002788] 1H NMR (DMSOd6): 7.63 (1 H, m), 7.21 (1 H, br t, J = 9.0 Hz), 5.11 (0.6 H, m), 4.72 (0.4 H, m), 4.11 (1 H, br d, J = 12.2 Hz), 4.0 - 3.51 (7 H, m), 3.32 (3 H , 2 s), 2.96 (1.8 H, s), 2.76 (2.2 H, m), 2.25 (0.4 H, m), 2.12 (0.6 H, m), 1.89 (0.4 H, m), 1.79 (0.6 H, m), 1.68 (1 H, m), 1.27 (1 H, m). 13

[002789] C NMR (DMSOd6): 168.3, 167.6, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.9, 156.8, 156.2, 156.1, 130.4, 130.3, 130.2, 117, 117, 116.9, 116.8, 116.8, 116.6, 116.4, 115.8, 115, 7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 69.3, 69.3, 67.1, 67.1, 67.1, 64.9, 56.6, 53, 52.2, 31.5, 31.5, 29.9, 29.9, 29.9, 29.8, 29.5, 29.5, 29.3, 29.2, 27.7, 27.6, 25.7, 21.8, 21.7, 21.2, 21.1.

[002790] Example 443: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N- (tetrahydro-2H-pyran-4-yl) acetamide

[002791] The compound was prepared in an analogous way to Example 32 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3 , 5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated like a light beige solid.

[002792] 1H NMR (DMSOd6): 7.64 (1 H, m), 7.21 (1 H, br t, J = 9.1 Hz), 4.49 (0.6 H, m), 4.11 (1 H, dd, J = 12.2, 2.2 Hz), 4.02 (0.4 H, m), 3.98-3.74 (4.8 H, m), 3 , 38 (2.2 H, m), 3.32 (3 H, 2 s), 2.92 (1.8 H, s), 2.81 (0.4 H, br dd, J = 8, 3, 4.3 Hz), 2.76 (0.6 H, br d, J = 4.3, 8.3 Hz), 2.74 (1.2 H, s), 1.87-1, 58 (4 H, m), 1.44 (1 H, m), 1.25 (1 H, m). 13

[002793] C NMR (DMSOd6): 167.7, 167.6, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.8, 156.8, 156.2, 156.1, 130.4, 130.3, 130.3, 130.2, 117.1, 116.9, 116.8, 116.7, 116.5, 115.8, 115, 7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 66.5, 66.5, 66.3, 53, 52.2, 31.5, 31, 5, 30.2, 30.2, 30.1, 29.6, 29.3, 29.2, 29.1, 27.1, 25.7, 25.7, 21.9, 21.7, 21.2, 21.2, 21.2.

[002794] Example 444: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1- (isoxazolidin-2-yl) ethan-1-one

[002795] The compound was prepared analogously to Example 168 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as an off-white solid.

[002796] 1H NMR (DMSOd6): 7.62 (1 H, td, J = 8.8, 5.6 Hz), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 11.5, 9.2 Hz), 3.97 (2 H, t, J = 6.8 Hz), 3.81 ( 1 H, dd, J = 11.6, 7.8 Hz), 3.75 (2 H, br s), 3.59 (2 H, m br), 3.39 (3 H, s), 3 , 30 (1 H, dd, J = 9.3, 15.9 Hz), 2.90 (1 H, dd, J = 15.8, 8.1 Hz), 2.26 (2 H, quin, J = 7.1 Hz). 13

[002797] C NMR (DMSOd6): 168.5, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 129.7, 129.7, 128.8, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 115.5, 113.3, 113.2, 113.1, 113.1, 69.3, 49.5, 43.3, 34.7, 31.5, 29.1, 28.5, 27.2.

[002798] Example 445: (R) -2- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -1-morpholinoetan-1-one

[002799] The compound was prepared in an analogous manner to Example 32 from (R) -2- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetra -hydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002800] 1H NMR (DMSOd6): 7.41 (1 H, m), 7.14 (2 H, t, J = 8.1 Hz), 4.41 (1 H, quin, J = 8, 7 Hz), 4.22 (1 H, m), 3.78 (1 H, dd, J = 11.4, 8.1 Hz), 3.75 (2 H, s), 3.60 (2 H, m), 3.55 (2 H, m), 3.49 (2 H, m), 3.44 (2 H, m), 3.36 (3 H, m), 3.25 (1 H, dd, J = 9.3, 15.9 Hz), 2.86 (1 H, dd, J = 15.7, 8.5 Hz). 13

[002801] C NMR (DMSOd6): 166.8, 161.6, 161.5, 160, 159.9, 156.3, 129.8, 129.7, 129.7, 128.3, 116, 6, 116.5, 116.4, 116.2, 112.3, 112.2, 112.1, 112.1, 66, 66, 49.6, 45.6, 41.7, 34.4, 31.5, 29.3, 28.8.

[002802] Example 446: 2 - ((R) -6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002803] The compound was prepared in an analogous manner to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (2,6- difluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002804] 1H NMR (DMSOd6): 8.36 (1 H, br d, J = 6.6 Hz), 7.41 (1 H, tt, J = 8.4, 6.5 Hz), 7 , 14 (2 H, m), 4.41 (1 H, quin, J = 8.8 Hz), 4.22 (2 H, m), 3.77 (2 H, m), 3.72 ( 1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.3, 5.6 Hz), 3.46 (1 H, dd, J = 8 , 9, 3.7 Hz), 3.43 (2 H, s), 3.40 (3 H, s), 3.26

(1 H, dd, J = 15.7, 9.2 Hz), 2.88 (1 H, dd, J = 15.7, 8.5 Hz), 2.08 (1 H, m), 1 , 71 (1 H, m). 13

[002805] C NMR (DMSOd6): 167.6, 161.6, 161.5, 160, 159.9, 156.2, 129.8, 129.8, 129.7, 128.5, 116, 6, 116.4, 116.4, 116.3, 112.3, 112.2, 112.1, 112.1, 72.4, 66.3, 49.8, 49.6, 34.4, 32, 31.5, 31.1, 29.3.

[002806] Example 447 (R) -2- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2- c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002807] The compound was prepared analogously to Example 32 from (R) -2- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetra -hydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002808] 1H NMR (DMSOd6): 8.11 (1 H, br d, J = 7.5 Hz), 7.41 (1 H, m), 7.14 (2 H, m), 4, 41 (1 H, quin, J = 8.7 Hz), 4.21 (1 H, dd, J = 10.8, 9.8 Hz), 3.77 (4 H, m), 3.42 ( 2 H, m), 3.40 (3 H, s), 3.33 (1H, m), 3.26 (1 H, dd, J = 15.7, 9.2 Hz), 2.88 ( 1 H, dd, J = 15.7, 8.5 Hz), 1.69 (2 H, m), 1.38 (2 H, m). 13

[002809] C NMR (DMSOd6): 166.9, 161.6, 161.5, 160, 159.9, 156.2, 129.8, 129.8, 129.7, 128.5, 116, 6, 116.5, 116.3, 112.3, 112.2, 112.1, 112.1, 65.8, 49.6, 45.2, 34.4, 32.4, 31.5, 31.3, 29.3.

[002810] Example 448: (R) -2- (6- (2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2 -c] imidazol-1-yl) -N-methyl-N- (oxetan-3-

il) acetamide

[002811] The compound was prepared analogously to Example 32 from (R) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (2,6-difluorophenyl) -3 - thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002812] 1H NMR (DMSOd6): 7.41 (1 H, m), 7.13 (2 H, m), 5.24 (1 H, m), 4.72, 4.64, 4, 59 (4 H, m), 4.40 (1 H, m), 4.22 (1 H, m), 3.79 (1 H, m), 3.75 (2 H, 2 s), 3 , 34 (3 H, s), 3.22 (1 H, m), 3.11 (1.8 H, s), 3.03 (1.2 H, s), 2.83 (1 H, m). 13

[002813] C NMR (DMSOd6): 168.6, 167.8, 161.6, 161.5, 160, 159.9, 156.2, 129.8, 129.7, 129.7, 128, 5, 128.3, 116.6, 116.5, 116.4, 116.3, 116.1, 112.3, 112.2, 112.1, 112.1, 74.6, 74.6, 74.2, 74.2, 51, 49.6, 49.2, 34.4, 31.5, 31.5, 30.7, 29.6, 29.3, 29.2, 29.2, 27.9.

[002814] Example 449: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - ((S) -1-methyl-5-oxopyrrolidin-3-yl) acetamide

[002815] The compound was prepared analogously to Example 22 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002816] 1H NMR (DMSOd6): 8.54 (1 H, br d, J = 6.6 Hz), 7.73 (1 H, td, J = 8.4, 5.7 Hz), 7 , 18 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.28 (1 H, m), 4.22 (1 H, dd, J = 11.4 , 9.2 Hz), 3.79 (1 H, dd, J = 11.6, 7.8 Hz), 3.60 (1 H, dd, J = 10.2, 7.0 Hz), 3 , 43 (2 H, d, J = 2.6 Hz), 3.39 (3 H, s), 3.28 (1 H, dd, J = 9.6, 15.9 Hz), 3.11 (1 H, dd, J = 10.3, 3.5 Hz), 2.88 (1 H, dd, J = 15.8, 8.1 Hz), 2.70 (3 H, s), 2 , 58 (1 H, ddd, J = 16.9, 8.5, 0.7 Hz), 2.11 (1 H, dd, J = 16.9, 4.3 Hz). 13

[002817] C NMR (DMSOd6): 171.7, 167.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.5, 118.8, 118.7, 118.5, 116.1, 113.8, 113.6, 104.1, 104.1, 103, 9, 55.1, 49.6, 42.5, 36.8, 34.8, 31.5, 31.1, 29.2, 28.9.

[002818] Example 450: (S) -1- (2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7- tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) pyrrolidine-3-carbonitrile

[002819] The compound was prepared analogously to Example 25 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (3-bromo- 2,6-difluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002820] 1H NMR (DMSOd6): 7.72 (1 H, m), 7.16 (1 H, t, J = 9.4 Hz),

4.44 (1 H, m), 4.23 (1 H, dd, J = 11.4, 9.2 Hz), 3.89-3.73 (2 H, m), 3.73-3 , 58 (3.5 H, m), 3.55 (1 H, m), 3.49-3.37 (1.5 H, m), 3.37 (3 H, s), 3.29 (1 H, m), 2.87 (1 H, m), 2.31 (0.5 H, m), 2.22 (1 H, m), 2.09 (0.5 H, m) . 13

[002821] C NMR (DMSOd6): 166.6, 166.4, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.5, 128.4, 121.1, 120.9, 118.9, 118.8, 118.8, 118.7, 118.6, 118, 6, 115.9, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 49.6, 48.7, 48.6, 44.8, 44, 6, 34.8, 34.8, 31.5, 30.2, 30.1, 29.6, 29.2, 28.1, 28, 26.5.

[002822] Example 451: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N - (((R) - tetrahydrofuran-3-yl) acetamide

[002823] The compound was prepared analogously to Example 34 from (S) -2- (2-methyl-6- (3-bromo-2,6-difluorophenyl) -3-thioxo-2,5-acid, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002824] 1H NMR (DMSOd6): 7.72 (1 H, m), 7.16 (1 H, s), 5.09 (0.6 H, m), 4.65 (0.4 H , m), 4.43 (1 H, m), 4.22 (1 H, dd, J = 11.3, 9.4 Hz), 3.92 (1 H, m), 3.81 (1 , 8 H, m), 3.69 (2.2 H, m), 3.63 (1 H, m), 3.56 (1 H, m), 3.36 (3 H, m), 3 , 25 (1 H, m), 2.93 (1.8 H, s), 2.85 (1 H, m), 2.74 (1.2 H, s), 2.21 (0.4 H, m), 2.09 (0.6 H, m), 1.86 (0.4 H, m), 1.76 (0.6 H, m). 13

[002825] C NMR (DMSOd6): 168.2, 167.6, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 156.2, 156.1, 155.9, 155.9, 132.5, 132.4, 128.3,

128.1, 118.9, 118.8, 118.6, 116.5, 116.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 69.4, 69.2, 67.1, 67, 56.6, 53, 49.5, 34.8, 34.8, 31.5, 31.5, 29.9, 29.8, 29, 7, 29.4, 29.3, 29.2, 29.2, 27.6.

[002826] Example 452: (S) -1- (2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) -N, N-dimethylpiperidine-4-carboxamide

[002827] The compound was prepared analogously to Example 25 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (3-bromo- 2,6-difluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one using DIPEA as a base and isolated as a cream powder .

[002828] 1H NMR (DMSOd6): 7.72 (1 H, td, J = 8.3, 5.9 Hz), 7.16 (1 H, t, J = 9.1 Hz), 4, 44 (1 H, quin, J = 8.5 Hz), 4.35 (1 H, m), 4.22 (1 H, dd, J = 11.4, 9.3 Hz), 3.91 ( 1 H, br d, J = 12.6 Hz), 3.80 (1 H, m), 3.75 (2 H, s), 3.36 (3 H, m), 3.26 (1 H , m), 3.11 (1 H, m), 3.03 (3 H, s), 2.87 (2 H, m), 2.80 (3 H, s), 2.67 (1 H , m), 1.65 (2 H, m), 1.53 (1 H, m), 1.33 (1 H, m). 13

[002829] C NMR (DMSOd6): 173.5, 166.2, 166.2, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.2, 118.8, 118.7, 118.6, 116.6, 113.8, 113.8, 113.6, 113, 6, 104.1, 104, 103.9, 103.9, 49.5, 44.7, 40.8, 40.8, 37.1, 36.6, 35, 34.8, 31.5, 29.2, 29,

28.9, 28.6, 27.9.

[002830] Example 453: 1- (2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro- 3H-pyrrolo [1,2-c] imidazol-1-yl) acetyl) -N, N-dimethylpyrrolidine-3-carboxamide

[002831] The compound was prepared analogously to Example 25 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (3-bromo- 2,6-difluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002832] 1H NMR (DMSOd6): 7.72 (1 H, m), 7.16 (1 H, t, J = 9.4 Hz), 4.44 (1 H, m), 4.22 (1 H, dd, J = 11.4, 9.3 Hz), 3.79 (1 H, br dd, J = 11.4, 7.8 Hz), 3.75-3.41 (5, 5 H, m), 3.38 (3 H, s), 3.41 - 3.21 (2.5 H, m), 3.03 - 3.01 (3 H, 3 s), 2.88 (1 H, m), 2.83-2.79 (3 H, 4 s), 2.12 (0.5 H, m), 2.04 (0.5 H, m), 1.99 ( 0.5 H, m), 1.85 (0.5 H, m).

[002833] 13C NMR (DMSOd6): 171.7, 171.3, 171.3, 166.1, 166, 166, 166, 160.8, 160.8, 159.2, 159.1, 157, 6, 157.5, 156.2, 156.2, 155.9, 155.9, 132.5, 132.4, 128.3, 118.9, 118.8, 118.8, 118.8, 118.8, 118.7, 118.7, 118.6, 118.6, 118.6, 116.2, 116.2, 116.1, 116.1, 113.8, 113.8, 113, 6, 113.6, 104.1, 104, 103.9, 103.9, 49.5, 49.5, 48.7, 48.4, 45.8, 45.3, 45.2, 40, 2, 38.3, 38.3, 36.7, 35.1, 35.1, 35, 34.8, 34.8, 31.5, 30.3, 30.3, 30.3, 30, 2, 29.2, 29.1, 29, 27.5.

[002834] Example 454: (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N-methyl-N- (oxetan-3-yl) acetamide

[002835] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-6- (3-bromo-2,6- difluorophenyl) -3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002836] 1H NMR (DMSOd6): 7.72 (1 H, td, J = 8.4, 5.9 Hz), 7.17 (1 H, m), 5.24 (1 H, m) , 4.72 (1.33 H, m), 4.64 (1.33 H, m), 4.59 (1.33 H, m), 4.43 (1 H, m), 4.22 (1 H, m), 3.75 (3 H, m), 3.33 (3H, s), 3.23 (1 H, m), 3.11 (1.8 H, s), 3, 03 (1.2 H, s), 2.82 (1 H, m). 13

[002837] C NMR (DMSOd6): 168.6, 167.8, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.4, 128.2, 118.9, 118.8, 118.6, 116.2, 116.1, 113.8, 113.8, 113, 6, 113.6, 104.1, 104, 103.9, 103.9, 74.6, 74.6, 74.2, 74.2, 51, 49.6, 49.2, 34.8, 31.5, 31.5, 30.7, 29.6, 29.3, 29.2, 29.1, 27.9.

[002838] Example 455: N-methyl-2 - ((R) -2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H -pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) - tetrahydrofuran-3-yl) acetamide

[002839] The compound was prepared analogously to Example 34 from (R) -2- (2-methyl-6- (2,3,6-trifluorophenyl) -3-thioxo-2,5,6 acid, 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002840] 1H NMR (DMSOd6): 7.47 (1 H, m), 7.18 (1 H, m), 5.09 (0.6 H, m), 4.66 (0.4 H , m), 4.43 (1 H, m), 4.24 (1 H, m), 3.92 (1 H, m), 3.82 (1.8 H, m), 3.71 ( 2.2 H, m), 3.62 (1 H, m), 3.56 (1 H, m), 3.33 (3 H, 2 s), 3.27 (1 H, m), 2 , 93 (1.8 H, s), 2.86 (1 H, m), 2.74 (1.2 H, s), 2.21 (0.4 H, m), 2.10 (0 , 6 H, m), 1.86 (0.4 H, m), 1.79 (0.6 H, m). 13

[002841] C NMR (DMSOd6): 168.2, 167.6, 157, 156.9, 156.9, 156.2, 156.2, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.4, 147.4, 147.4, 145.9, 145.9, 145.8, 128.2, 128.1, 118.9, 118.8, 118.8, 118.8, 118.7, 116.6, 116.5, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 69.4, 69.3, 67.1, 67.1, 56.5, 53, 49.4, 34.8, 31.5, 31.5, 30, 29.7, 29.7, 29.4, 29.3, 29.1, 29.1, 27.6.

[002842] Example 456: (S) -6- (3-bromo-2,6-difluorophenyl) -1- (2-hydroxyethyl) -2-methyl-2,5,6,7-tetrahydro-3H- pyrrole [1,2-c] imidazole-3-thione

[002843] The compound was prepared analogously to Example 8 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic (analogous to Example 229) and isolated as a cream powder.

[002844] 1H NMR (DMSOd6): 7.72 (1 H, m), 7.17 (1 H, m), 4.78 (1 H, t, J = 5.3 Hz), 4.43 (1 H, quin, J = 8.7 Hz), 4.20 (1 H, dd, J = 11.5, 9.3 Hz), 3.78 (1 H, dd, J = 11.6, 7.9 Hz), 3.58 (2 H, td, J = 6.5, 5.3 Hz), 3.43 (3 H, s), 3.31 (1 H, m), 2.94 (1 H, dd, J = 15.7, 8.2 Hz), 2.65 (2 H, t, J = 6.4 Hz). 13

[002845] C NMR (DMSOd6): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156, 155.9, 155.8, 132.5, 132, 4, 127.5, 119.4, 118.8, 118.6, 118.5, 113.8, 113.8, 113.6, 113.6, 104.1, 104.1, 103.9, 103.9, 58.9, 49.3, 34.8, 31.3, 29.3, 27.7.

[002846] Example 457: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N- (1-methyl-6-oxopiperidin-3-yl) acetamide

[002847] The compound was prepared analogously to Example 22 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5, 6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a cream powder.

[002848] 1H NMR (DMSOd6): 78.35 (1 H, m), 7.74 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.5, 9.2 Hz), 4.04 (1 H, m), 3.79 (1 H, dd, J = 11 , 7, 7.7 Hz), 3.47 (2 H, m), 3.42 (1 H, m), 3.41 (3 H, s), 3.28 (1 H, m), 3 , 08 (1 H, m), 2.88 (1 H, dd, J = 15.9, 8.0 Hz), 2.77 (3 H, 2 s), 2.28 (2 H, m) , 1.86 (1 H, m), 1.75 (1 H, m). 13

[002849] C NMR (DMSOd6): 167.7, 167.6, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.5, 128.4, 118.8, 118.7, 118.6, 116.3, 113.8, 113.8, 113.6, 113, 6, 104.1, 104.1, 103.9, 103.9, 52.9, 49.6, 43.4, 43.4, 34.8, 33.9, 31.5, 31.1, 31.1, 29.2, 29, 29, 26.1.

[002850] Example 458: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -1- (3- (fluoromethyl) pyrrolidin-1-yl) ethan-1-one

[002851] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002852] 1H NMR (DMSOd6): 7.72 (1 H, m), 7.16 (1 H, t, J = 9.4 Hz), 4.44 (3 H, m), 4.22 (1 H, dd, J = 11.4, 9.2 Hz), 3.80 (1H, m), 3.70 (0.5 H,

m), 3.65 (2 H, d, J = 5.9 Hz), 3.61 (0.5 H, m), 3.48 (1.5 H, m), 3.37 (3 H , 2 s), 3.28 (2 H, m), 3.11 (0.5 H, m), 2.85 (1 H, m), 2.65 (0.5 H, m), 2 , 56 (0.5 H, m), 2.04 (0.5 H, m), 1.92 (0.5 H, m), 1.75 (0.5 H, m), 1.62 (0.5 H, m). 13

[002853] C NMR (DMSOd6): 166.3, 166.3, 160.8, 160.7, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.3, 128.3, 128.3, 118.9, 118.8, 118.7, 116.2, 113.8, 113.8, 113, 6, 113.6, 104.1, 104.1, 103.9, 103.9, 84.8, 84.8, 83.7, 83.7, 49.6, 48, 47.9, 47, 2, 47.2, 45.4, 45, 37.3, 37.2, 37.1, 37.1, 34.8, 31.5, 31.5, 30.3, 30.1, 30, 1, 29.2, 27.2, 27.1, 25.4, 25.4, 25.4, 25.4.

[002854] Example 459: 2 - ((S) -6- (3-bromo-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazol-1-yl) -N - (((S) -tetrahydrofuran-3-yl) acetamide

[002855] The compound was prepared analogously to Example 32 from (S) -1- (1H-imidazol-1-yl) -2- (2-methyl-3-thioxo-6- (3-bromo- 2,6-difluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) ethan-1-one and isolated as a cream powder.

[002856] 1H NMR (DMSOd6): 8.36 (1 H, d, J = 6.6 Hz), 7.72 (1 H, m), 7.16 (1 H, t, J = 9, 3 Hz), 4.44 (1 H, quin, J = 8.6 Hz), 4.22 (2 H, m), 3.78 (2 H, m), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.3, 5.6 Hz), 3.46 (1 H, dd, J = 8.9, 3, 5 Hz), 3.43 (2 H, s), 3.40 (3 H, s), 3.28 (1 H, dd, J = 15.8, 9.5 Hz), 2.88 (1 H, dd, J = 15.8, 7.9 Hz), 2.08 (1 H, dq, J = 12.8, 7.6 Hz), 1.71 (1 H, m).

[002857] C NMR (DMSOd6): 167.6, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.4, 118.8, 118.7, 118.6, 116.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 1, 103.9, 103.9, 72.4, 66.3, 49.8, 49.6, 34.8, 32, 31.5, 31.1, 29.2.

[002858] Example 460: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2- (methyl-d3) - 3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) -1- morpholinoetan-1-one

[002859] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxy-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002860] 1H NMR (DMSOd6): 7.61 (1 H, td, J = 8.8, 5.6 Hz), 7.22 (1 H, td, J = 9.5, 1.6 Hz ), 4.44 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, dd, J = 11.5, 9.2 Hz), 3.80 (1 H, dd, J = 11.6, 7.8 Hz), 3.74 (2 H, s), 3.60 (2 H, m), 3.55 (2 H, m), 3.49 (2 H, m) , 3.44 (2 H, m), 3.27 (1 H, dd, J = 15.8, 9.4 Hz), 2.86 (1 H, dd, J = 15.8, 7.9 Hz). 13

[002861] C NMR (DMSOd6): 166.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.2, 118.9, 118.8, 118.6, 116.2, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 66, 66, 49.5, 45.6, 41.7, 34.8, 29.2, 28.8.

[002862] Example 461: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-

(methyl-d3) -3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) -N - ((S ) -tetrahydrofuran-3-yl) acetamide

[002863] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002864] 1H NMR (DMSOd6): 8.39 (1 H, d, J = 6.7 Hz), 7.58 (1 H, m), 7.56 (1 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.26 (1 H, m), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.80 (2 H, m), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3.51 (2 H, m), 3.49 (1H, dd, J = 3.6, 8.9 Hz), 2.88 (1 H , dd, J = 8.4, 4.2 Hz), 2.10 (1 H, m), 1.74 (1 H, m), 1.70 (1 H, dd, J = 8.4, 5.4 Hz), 1.13 (1 H, m). 13

[002865] C NMR (DMSOd6): 167.7, 161.8, 160.2, 156.8, 133.1, 133, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.9, 116.2, 116.2, 116.1, 72.4, 66.3, 52.4, 49.8, 32, 31.5, 31, 22.1, 20.7.

[002866] Example 462: acid 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2- (methyl-d3) -3-thioxo-2,3,5,5a, 6, 6a-hexahydrocyclopropa [3,4] pyrrole [1,2-c] imidazol-1-yl) acetic

[002867] The compound was prepared analogously to Example 2 from (1R, 5S) -3- (tert-butoxycarbonyl) -5- (5-bromo-2-fluorophenyl) - 3-azabicyclo [3.1.0 ] hexane-2-carboxylic. The product was isolated as a beige solid.

[002868] 1H NMR (DMSOd6): 12.78 (1 H, br s), 7.57 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz ), 4.16 (1 H, d, J = 11.9 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.75 (2 H, m), 2.97 ( 1 H, dd, J = 8.5, 4.1 Hz), 1.70 (1 H, dd, J = 8.4, 5.4 Hz), 1.13 (1 H, m). 13

[002869] C NMR (DMSOd6): 170.9, 161.8, 160.2, 157, 133, 133, 132.4, 132.3, 131.2, 129.1, 129, 118, 117, 9, 116.2, 116.2, 115.2, 52.5, 52.4, 31.5, 29.7, 22.1, 20.6. Example 463: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2- (methyl-d3) -3-thioxo-2,3,5,5a, 6,6a-hexa- hydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) - N- (tetrahydro-2H-pyran-4-yl) acetamide

[002870] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002871] 1H NMR (DMSOd6): 8.14 (1 H, d, J = 7.5 Hz), 7.58 (1 H, m), 7.56 (1 H, ddd, J = 6, 5, 4.4, 2.3 Hz), 7.24 (1 H, dd, J = 10.2, 8.7 Hz), 4.14 (1 H, d, J = 11.9 Hz), 3.85 (1 H, d, J = 12.2 Hz), 3.82 (2 H, m), 3.77 (1 H, m), 3.49 (2 H, m), 3.33 (2H, m), 2.88 (1 H, dd, J = 8.4, 3.9 Hz), 1.71 (3 H, m), 1.40 (2 H, m), 1.13 (1 H, t, J = 4.8 Hz). 13

[002872] C NMR (DMSOd6): 167, 161.8, 160.2, 156.8, 133.1, 133.1, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.9, 116.2, 116.2, 116.2, 65.9, 52.4, 45.2, 32.4, 32.4, 31.5, 31.2, 22.1, 20.7.

[002873] Example 464: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2- (methyl-d3) -3-thioxo-2,3,5,5a, 6.6a -hexa-hydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydro-2H-pyran-3-yl) acetamide

[002874] The compound was prepared analogously to Example 34 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3 acid, 5.5a, 6.6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a beige solid.

[002875] 1H NMR (DMSOd6): 8.14 (1 H, br d, J = 7.5 Hz), 7.58 (1 H, dd, J = 6.7, 2.6 Hz), 7 , 56 (1 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.2 Hz), 3.71 (2 H, m), 3.65 (1 H, dt, J = 11.1, 4.3 Hz), 3.51 (2 H, m), 3.39 (1 H, m), 3.14 (1 H, m), 2.88 (1 H, dd, J = 8.5, 4.1 Hz), 1.83 ( 1 H, br d, J = 12.0 Hz), 1.68 (2 H, m),

1.50 (2 H, m), 1.12 (1 H, t, J = 4.8 Hz). 13

[002876] C NMR (DMSOd6): 167.4, 161.8, 160.2, 156.8, 133.1, 133, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.9, 116.2, 116.2, 116.1, 70.1, 67, 52.4, 45.2, 31.5, 31.1, 28.6, 23.9, 22, 1, 20.7.

[002877] Example 465: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2- (methyl-d3) -3-thioxo-2,3,5,5a, 6.6a -hexa-hydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide

[002878] The compound was prepared analogously to Example 32 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo- 2,3,5 , 5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as a beige solid.

[002879] 1H NMR (DMSOd6): 8.40 (1 H, d, J = 6.7 Hz), 7.58 (1 H, m), 7.56 (1 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.26 (1 H, m), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.80 (2 H, m), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3.51 (2 H, m), 3.49 (1H, dd, J = 3.6, 8.9 Hz), 2.88 (1 H , dd, J = 8.4, 4.2 Hz), 2.10 (1 H, m), 1.74 (1 H, m), 1.70 (1 H, dd, J = 8.4, 5.4 Hz), 1.13 (1 H, m). 13

[002880] C NMR (DMSOd6): 167.7, 161.8, 160.2, 156.8, 133.1, 133, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.9, 116.2, 116.2, 116.1, 72.3, 66.3, 52.4, 49.8, 32.1, 31.5, 31, 22.1, 20, 7.

[002881] Example 466: 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N - ((R) -tetrahydrofuran-3-yl) acetamide

[002882] The compound was prepared analogously to Example 34 from 2 - ((5aS, 6aR) -5a- (5-bromo-2-fluorophenyl) -2-methyl-3-thioxo-2,3 acid, 5.5a, 6.6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a beige solid.

[002883] 1H NMR (DMSOd6): 7.58 (2 H, m), 7.24 (1 H, m), 5.11 (0.6 H, m), 4.72 (0.4 H , m), 4.15 (1 H, d, J = 12.1 Hz), 4.0-3.51 (7 H, m), 3.31 (3 H, 2 s), 2.98 ( 1.8 H, s), 2.86 (1 H, m), 2.76 (1.2 H, s), 2.24 (0.4 H, m), 2.12 (0.6 H , m), 1.89 (0.4 H, m), 1.81 (0.6 H, m), 1.70 (1 H, m), 1.13 (1 H, m). 13

[002884] C NMR (DMSOd6): 168.3, 167.7, 161.8, 160.2, 160.2, 156.9, 156.8, 133.1, 133.1, 133, 132, 4, 132.3, 130.8, 130.7, 129.2, 129.1, 129.1, 129, 118, 117.9, 116.2, 116.2, 116.2, 116.1, 69.4, 69.3, 67.2, 67.1, 56.6, 53, 52.4, 31.6, 31.6, 31.5, 31.5, 29.9, 29.8, 29.8, 29.4, 29.3, 22.1, 20.7.

[002885] Example 467: 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexa -hydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N - ((R) -tetrahydrofuran-3-yl) acetamide

[002886] The compound was prepared analogously to Example 34 from 2 - ((5aS, 6aR) -5a- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2 acid, 3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a beige solid.

[002887] 1H NMR (DMSOd6): 7.64 (1 H, m), 7.21 (1 H, br t, J = 9.0 Hz), 5.11 (0.6 H, m), 4.71 (0.4 H, m), 4.11 (1 H, br d, J = 12.2 Hz), 4.0 - 3.51 (7 H, m), 3.32 (3 H , 2 s), 2.96 (1.8 H, s), 2.76 (2.2 H, m), 2.24 (0.4 H, m), 2.12 (0.6 H, m), 1.88 (0.4 H, m), 1.80 (0.6 H, m), 1.69 (1 H, m), 1.26 (1 H, m). 13

[002888] C NMR (DMSOd6): 168.3, 167.6, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.9, 156.8, 156.2, 156.1, 130.4, 130.3, 130.3, 117.1, 116.9, 116.8, 116.6, 116.5, 115.8, 115.7, 115, 6, 115.6, 112.9, 112.9, 112.8, 112.8, 69.4, 69.3, 67.2, 67.1, 56.6, 53, 52.2, 31, 5, 31.5, 29.9, 29.9, 29.8, 29.5, 29.3, 27.7, 25.7, 21.8, 21.7, 21.2, 21.2.

[002889] Example 468: 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3,5,5a, 6,6a-hexahydrocyclopropa [3,4] pyrrolo [1,2- c] imidazol-1-yl) -N-methyl-N - ((R) -tetrahydrofuran-3-yl) acetamide

[002890] The compound was prepared in an analogous manner to Example 34 from 2 - ((5aS, 6aR) -5a- (5-chloro-2-fluorophenyl) -2-methyl-3-thioxo-2,3 acid, 5.5a, 6.6a-hexahydrocyclopropa [3,4] pyrrolo [1,2-c] imidazol-1-yl) acetic and isolated as a beige solid.

[002891] 1H NMR (DMSOd6): 7.45 (2 H, m), 7.30 (1 H, m), 5.11 (0.6 H, m), 4.72 (0.4 H , m), 4.15 (1 H, br d, J = 11.9 Hz), 4.0-3.52 (7 H, m), 3.31 (3 H, 2 s), 2.97 (1.8 H, s), 2.86 (1 H, m), 2.76 (1.2 H, s), 2.24 (0.4 H, m), 2.12 (0.6 H, m), 1.89 (0.4 H, m), 1.80 (0.6 H, m), 1.70 (1 H, m), 1.13 (1 H, m). 13

[002892] C NMR (DMSOd6): 168.3, 167.7, 161.3, 161.3, 159.7, 159.7, 156.9, 156.8, 130.8, 130.7, 130.2, 130.2, 129.4, 129.4, 128.8, 128.7, 128.7, 128.6, 128.6, 128.3, 117.6, 117.4, 116, 3, 116.2, 69.4, 69.3, 67.2, 67.1, 56.6, 53.1, 52.4, 31.7, 31.6, 31.5, 31.5, 30, 29.8, 29.8, 29.5, 29.3, 27.7, 22.1, 20.7.

[002893] Example 469: (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2- (methyl-d3) - 3-thioxo-2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazol-1-yl) -N- (tetrahydro-2H-pyran-4-yl) acetamide

[002894] The compound was prepared analogously to Example 32 from (S) -2- (6- (3-chloro-2,6-difluorophenyl) -2-methyl-3-thioxo-2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (1H-imidazol-1-yl) ethan-1-one and isolated as an off-white solid.

[002895] 1H NMR (DMSOd6): 8.11 (1 H, d, J = 7.5 Hz), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7, 22 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.6, 9.2 Hz), 3.81 ( 3 H, m), 3.74 (1 H, m), 3.42 (2 H, m), 3.33 (2 H, m), 3.29 (1 H, dd, J = 9.0 , 15.9 Hz), 2.89 (1 H, dd, J = 15.9, 8.0 Hz), 1.69 (2 H, m), 1.38 (2 H, m). 13

[002896] C NMR (DMSOd6): 166.8, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.7, 118.6, 116.4, 116, 115.9, 113.2, 113.1, 65.8, 49.5, 45.2, 34.7, 32.4, 31.3, 29.2.

[002897] Example 470: R) -6- (2,3,6-trifluoropheni) -1- (2 - ((((R) -tetrahydrofuran-3-yl) amino) ethyl) -2,5,6 , 7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[002898] The compound was prepared analogously to Example 35 from 2 - ((R) -6- (2,3,6-trifluoropheni) -3-thioxo-2,5,6,7-tetrahydro -3H- pyrrolo [1,2-c] imidazol-1-yl) -N - ((R) -tetrahydrofuran-3-yl) acetamide and isolated as a cream powder.

[002899] 1H NMR (DMSOd6): 11.90 (1 H, br s), 9.24 (2 H, m), 7.49 (1 H, m), 7.19 (1 H, m) , 4.43 (1 H, quin, J = 8.8 Hz), 4.16 (1 H, dd, J = 11.2, 9.0 Hz), 3.92 (1 H, m), 3 , 88 (1 H, m), 3.82 (1 H, m), 3.75 (2 H, m), 3.65 (1 H, m), 3.32 (1 H, dd, J = 9.1, 15.5 Hz), 3.15 (2 H, m), 2.96 (1 H, br dd, J = 15.6, 8.7 Hz), 2.81 (2 H, br t, J = 7.6 Hz), 2.20 (1 H, m), 2.01 (1 H, m). 13

[002900] C NMR (DMSOd6): 157, 156.9, 155.9, 155.4, 155.3, 150.9, 149.1, 149.1, 149, 149, 147.6, 147, 5, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 129.3, 118.5, 118.5, 118.4, 118.3, 116.6, 116.5, 116.5, 116.4, 114.9, 112, 112, 112, 112, 111.9, 111.8, 111.8, 111, 8, 68.8, 66.4, 57.3, 48.3, 43.7, 35.7, 29, 28.8, 21.2.

[002901] Example 471: (R) -1- (3- (pyrrolidin-1-yl) propyl) -6- (2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro -3H-pyrrolo [1,2-c] imidazole-3-thione

[002902] The compound was prepared in an analogous manner to Example 35 from (R) -1- (pyrrolidin-1-yl) -3- (6- (2,3,5,6-tetrafluorophenyl) -3-thioxo - 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one and isolated as an off-white powder.

[002903] 1H NMR (DMSOd6): 11.81 (1 H, br s), 7.84 (1 H, m), 4.49 (1 H, m), 4.15 (1 H, dd, J = 11.7, 9.1 Hz), 3.76 (1 H, dd, J = 11.7, 7.6 Hz), 3.29 (1 H, dd, J = 15.6, 9, 3 Hz), 2.90 (1 H, dd, J = 15.7, 7.8 Hz), 2.38 (6 H, m), 2.33 (2 H, t, J = 7.1 Hz ), 1.66 (6 H, m). 13

[002904] C NMR (DMSOd6): 155, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145, 3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.5, 127.4, 120.6, 120.5, 120.4, 119, 6, 105.8, 105.7, 105.5, 54.6, 53.5, 48.3, 35.8, 29, 26.9, 23.1, 22.

[002905] Example 472: (R) -1- (3- (isopropylamino) propyl) fluorohydrate - 6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrole [1,2-c] imidazole-3-thione

[002906] The compound was prepared in an analogous manner to Example 35 from (R) -N-isopropyl-3- (3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propanamide and isolated as a light beige solid.

[002907] 1H NMR (DMSOd6): 11.85 (1 H, br s), 8.44 (2 H, br), 7.48 (1 H, qd, J = 9.4, 5.0 Hz ), 7.18 (1 H, m), 4.47 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, dd, J = 11.5, 9.2 Hz), 3.74 (1 H, dd, J = 11.7, 7.8 Hz), 3.31 (1 H, dd, J = 9.5, 15.8 Hz), 3.25 (1 H, m ), 2.91 (1 H, dd, J = 15.6, 7.8 Hz), 2.84 (2 H, m), 2.45 (2 H, t, J = 7.4 Hz), 1.83 (2 H, quin, J = 7.6 Hz), 1.19 (6 H, d, J = 6.6 Hz). 13

[002908] C NMR (DMSOd6): 156.9, 156.9, 155.4, 155.3, 155.3, 149.1, 149.1, 149, 149, 148.9, 147.6, 147.6, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 147.3, 147.3, 146, 145.9, 145.9, 145.9, 128.1, 119.1, 119, 119, 118.9, 118.2, 116.5, 116.5, 116.4, 116.4, 112, 112, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 49.5, 48.5, 43.2, 35.6, 29.1, 24.7, 21.2, 18.7, 18, 6.

[002909] Example 473: (R) -1- (2 - ((((tetrahydro-2H-pyran-4-yl) methyl) amino) ethyl) -6- (2,3,6-trifluorophenyl) hydrochloride -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[002910] The compound was prepared analogously to Example 35 from (R) -N - ((tetrahydro-2H-pyran-4-yl) methyl) -2- (3-thioxo-6- (2 , 3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide and isolated as a yellow solid.

[002911] 1H NMR (DMSOd6): 11.91 (1 H, s), 8.93 (2 H, m), 7.50 (1 H, m), 7.19 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.16 (1 H, dd, J = 11.5, 9.2 Hz), 3.86 (2 H, m), 3, 75 (1 H, dd, J = 11.5, 8.3 Hz), 3.32 (1 H, dd, J = 15.5, 9.2 Hz), 3.27 (2 H, td, J = 11.7, 2.1 Hz), 3.12 (2 H, m), 2.95 (1 H, dd, J = 15.6, 8.7 Hz), 2.82 (4 H, m ), 1.94 (1 H, m), 1.67 (2 H, m), 1.21 (2 H, qd, J = 12.2, 4.5 Hz). 13

[002912] C NMR (DMSOd6): 156.9, 156.9, 155.8, 155.3, 155.3, 129.2, 118.6, 118.5, 118.5, 118.4, 116.6, 116.5, 116.5, 116.4, 115, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 66.3, 51.9, 48, 3, 45.4, 35.7, 31.7, 30, 29, 20.8.

[002913] Example 474: (R) -2-methyl-1- (2- (pyrrolidin-1-yl) ethyl) -6- (2,3,6-trifluorophenyl) -2,5,6,7 fluorohydrate -tetrahydro-3H-pyrrolo [1,2- c] imidazole-3-thione

[002914] The compound was prepared analogously to Example 35 from (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -1- (pyrrolidin-1-yl) ethan-1-one and isolated as a light beige solid.

[002915] 1H NMR (DMSOd6): 9.65 (1 H, m), 7.49 (1 H, m), 7.19 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 9.3, 11.3 Hz), 3.82 (1 H, dd, J = 11.6, 7.9 Hz), 3 , 47 (3 H, s), 3.38 (1 H, dd, J = 9.4, 15.7 Hz), 3.25-2.95 (6 H, m), 3.00 (1 H , dd, J = 15.7, 8.2 Hz), 2.87 (2 H, m), 1.89 (4 H, m). 13

[002916] C NMR (DMSOd6): 156.9, 156.9, 156.5, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9,

145.9, 145.8, 145.8, 127.9, 118.8, 118.7, 118.7, 118.6, 117.4, 117.3, 116.5, 116.5, 116, 4, 116.4, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 53.3, 51.8, 49.3, 34.8, 31, 3, 29.3, 22.7, 21.6.

[002917] Example 475: (R) -1- (2 - (((((S) -tetrahydrofuran-2-yl) methyl) amino) ethyl) -6- (2,3,6-trifluorophenyl) hydrochloride -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[002918] The compound was prepared analogously to Example 35 from N - (((S) -tetrahydrofuran-2-yl) methyl) -2 - ((R) -3-thioxo-6- (2 , 3,6-trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide and isolated as a cream powder.

[002919] 1H NMR (DMSOd6): 11.90 (1 H, s), 8.92 (2 H, m), 7.49 (1 H, m), 7.19 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (2 H, m), 3.80 (1 H, dt, J = 8.1, 6.9 Hz), 3, 75 (1 H, dd, J = 11.6, 8.4 Hz), 3.71 (1 H, td, J = 7.8, 6.1 Hz), 3.30 (1 H, dd, J = 15.6, 9.1 Hz), 3.15 (2 H, m), 3.06 (1 H, m), 2.94 (1 H, dd, J = 8.6, 15.6 Hz ), 2.89 (1 H, m), 2.79 (2 H, t, J = 7.6 Hz), 2.00 (1 H, m), 1.85 (2 H, m), 1 , 55 (1 H, m). 13

[002920] C NMR (DMSOd6): 157, 156.9, 155.8, 155.4, 155.3, 149.1, 149.1, 149.1, 149, 149, 149, 147.6, 147.6, 147.5, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 146, 145.9, 145.9, 145.9, 129.2, 118.6, 118.5, 118.5, 118.4, 116.6, 116.5, 116.5, 116.4, 115, 112, 112, 112, 112, 111.9, 111.9, 111.8, 111.8, 73.7, 67.6, 50.3, 48.3, 45.3, 35.8, 29, 28.8, 25, 20.9.

[002921] Example 476: (R) -1- (2- (tert-butylamino) ethyl) -2-methyl-6- (2,3,6-trifluorophenyl) -2,5,6,7-tetra fluorohydrate -hydro-3H-pyrrolo [1,2-c] imidazole-

3-thion

[002922] The compound was prepared analogously to Example 35 from (R) -N- (tert-butyl) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) - 2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) acetamide and isolated as an off-white solid.

[002923] 1H NMR (DMSOd6): 8.61 (2 H, m), 7.50 (1 H, m), 7.21 (1 H, m), 4.44 (1 H, quin, J = 8.8 Hz), 4.24 (1 H, dd, J = 9.5, 11.2 Hz), 3.83 (1 H, dd, J = 11.6, 8.2 Hz), 3 , 48 (3 H, s), 3.42 (1 H, dd, J = 9.3, 15.5 Hz), 3.04 (1 H, dd, J = 8.5, 15.8 Hz) , 3.02 (2 H, m), 2.83 (2 H, m), 1.25 (9 H, br s). 13

[002924] C NMR (DMSOd6): 157, 156.5, 155.4, 149.2, 149.1, 147.6, 147.5, 147.5, 146.1, 146, 145.9, 128.1, 118.7, 118.6, 118.5, 117.2, 116.6, 116.5, 116.5, 116.4, 112, 111.8, 55.7, 49.3, 39.8, 34.8, 31.4, 29.1, 25.7, 22.2.

[002925] Example 477: (R) -2-methyl-1- (2 - ((((tetrahydro-2H-pyran-4-yl) methyl) amino) ethyl) -6- (2,3, 6-trifluorophenyl) -2,5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazole-3-thione

[002926] The compound was prepared analogously to Example 35 from (R) -2- (2-methyl-3-thioxo-6- (2,3,6-trifluorophenyl) -2,5,6,7 -tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) -N - ((tetrahydro-2H-pyran-4-yl) methyl) acetamide and isolated as a beige solid.

[002927] 1H NMR (DMSOd6): 8.87 (2 H, m), 7.49 (1 H, m), 7.19 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.23 (1 H, dd, J = 11.4, 9.3 Hz), 3.85 (2 H, m), 3.82 (1 H, dd, J = 11 , 7, 8.1 Hz), 3.47 (3 H, s), 3.39 (1 H, dd, J = 9.3, 15.7 Hz), 3.28 (2 H, td, J = 11.7, 2.1 Hz), 3.12 (2 H, m), 3.0 (1 H, dd, J = 8.3, 15.7 Hz), 2.97 (2 H, m ), 2.84 (2 H, q, J = 6.5 Hz), 1.94 (1 H, m), 1.67 (2 H, m), 1.22 (2 H, qd, J = 12.3, 4.8 Hz). 13

[002928] C NMR (DMSOd6): 157, 156.9, 156.6, 155.4, 155.3, 149.1, 149.1, 149.1, 149, 149, 147.6, 147, 5, 147.4, 147.4, 146, 145.9, 145.9, 145.9, 128.4, 118.7, 118.7, 118.6, 118.5, 116.7, 116, 6, 116.6, 116.5, 116.4, 112.1, 112, 112, 112, 111.9, 111.9, 111.8, 111.8, 66.3, 52.1, 49, 4, 45.2, 34.8, 31.9, 31.4, 30, 29.2, 20.8.

[002929] Example 478: (R) -1- (3- (pyrrolidin-1-yl) propyl) -6- (2,3,6-trifluorophenyl) -2,5,6,7-tetrahydrohydrate -3H-pyrrolo [1,2-c] imidazole-3-thione

[002930] The compound was prepared analogously to Example 35 from (R) -1- (pyrrolidin-1-yl) -3- (3-thioxo-6- (2,3,6-trifluorophenyl) -2 , 5,6,7-tetrahydro-3H-pyrrolo [1,2-c] imidazol-1-yl) propan-1-one and isolated as a light beige solid.

[002931] 1H NMR (DMSOd6): 11.84 (1 H, s), 9.83 (1 H, m), 7.48 (1 H, m), 7.19 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.4,

9.1 Hz), 3.74 (1 H, dd, J = 11.7, 8.1 Hz), 3.29 (1 H, dd, J = 9.0, 15.6 Hz), 3, 19-2.86 (4 H, br), 3.05 (2 H, m), 2.93 (1 H, dd, J = 15.6, 8.4 Hz), 2.43 (2 H, br t, J = 7.5 Hz), 1.94 (6 H, m). 13

[002932] C NMR (DMSOd6): 156.9, 156.9, 155.4, 155.3, 155.3, 149.1, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.3, 146, 145.9, 145.9, 128.1, 118.9, 118.8, 118.7, 118.7, 118.2, 116.6, 116.5, 116.4, 116.4, 112, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 53.2, 48.4, 35, 7, 29, 24.2, 22.6, 21.2. G. Dopamine-β-hydroxylase Inhibition Assay

[002933] The ability of a compound to inhibit DβH activity can be assessed using the following cell assay. For the purpose of the present invention, a compound is considered to be an "inhibitor if DβH" if it has activity in "% control" of ≤ 20% at 10 µM in this cell assay. The preferred compounds of the present invention (including almost all of the specific Examples above) show "% control" activity of ≤ 50% at 1.0 µM in this cell assay. The most preferred compounds of the present invention have "% control" activity of ≤ 20% to 1.0 µM in this cell assay. Especially preferred compounds of the present invention have "% control" activity of ≤ 50% to 100 µM. nM in this assay.

[002934] SK-N-SH cells (ATCC HTB-11), obtained from LGC Standards (Teddington, UK) were grown in Eagle's minimum essential medium supplemented with 25 mM Hepes, 100 U / mL of penicillin g, 0, 25 µg / mL amphotericin B, 100 µg / mL streptomycin and 10% fetal bovine serum gibco®. The cells were grown in T162 cm flasks (Corning, NI) in a humidified atmosphere of 5% CO2-95% air at 37 ° C. The fetal bovine serum was removed from the cells for 4 h before collection.

[002935] For the preparation of cell homogenates, the medium was removed and the cell monolayers were washed with 50 mM Tris-HCl pH 7.4. The cells were subsequently scraped from the flasks and resuspended in 50 mM Tris pH 7.4. The cell suspensions were homogenized with SilentCrusher M (Heidolph) for a short course and the resulting homogenates were aliquoted and stored frozen at -80 ° C.

[002936] Total protein was quantified in cell homogenates with BioRad Protein Assay (BioRad) using a standard BSA curve (50-250 µg / mL).

[002937] DβH activity was measured by a modification of the Nagatsu and Udenfriend method (Nagatsu, T. and S. Udenfriend: "Photometric assay of dopamine-hydroxylase activity in human blood." Clin. Chem. 18 (9): 980-983, 1972) which is based on the enzymatic hydroxylation of tyramine to octopamine. The octopamine formed is subsequently oxidized to p-hydroxybenzaldehyde and measured by spectrophotometry. Briefly, the reaction mixture (total volume 500 µL) contained: cell homogenate (75 µg total protein), sodium acetate pH 5.0 (200 mM), N-ethylmaleimide (30 mM), CuSO4 (5 µM), aqueous catalase solution (0.5 mg / mL), pargyline-HCl (1 mM), sodium fumarate (10 mM), ascorbic acid (10 mM), inhibitor or carrier and tyramine (25 mM). After a pre-incubation period of 10 min at 37 ° C, the reaction was initiated by the addition of tyramine. The reaction was carried out for 45 min at 37 ° C before termination with 50 µL of perchloric acid (2 M). The samples were centrifuged for 3 min at 16 100 g and the supernatants were subjected to solid phase extraction. Solid phase extraction was performed using SPE ISOLUTE SCX-3 cartridges (100 mg, 1 mL) or 96-well plates fixed with 2 mL of SPE ISOLUTE SCX-3 (100 mg) previously equilibrated with MilliQ water. The columns / plates were centrifuged at 150 g for 2 min. The eluate was discarded and the matrix was washed with 1 ml of water

MilliQ after which octopamine was eluted with 2x 0.25 ml of ammonium hydroxide (4 M). The oxidation of octopamine to p-hydroxybenzaldehyde was carried out for 6 min with 100 µL of sodium periodate (2%) and was stopped with 100 µL of sodium metabisulfite (10%). Absorbance was measured at 330 nm in a Spectramax microplate reader (Molecular Devices, Sunnyvale, CA). All enzymatic reactions were performed in duplicate.

[002938] The results are reported in the table below as activity in% control on the tested inhibitor concentration.

[002939] In addition, the ability of a compound to inhibit DβH activity can be assessed in human plasma using the following assay. For the purpose of the present invention, a compound is considered to be a "DβH inhibitor" if it exhibits "% control" activity of ≤ 20% at 10 µM in this assay. Preferred compounds of the present invention (including most of the specific Examples above) exhibit "% control" activity of ≤ 50% at 1.0 µM in this cell assay. The most preferred compounds of the present invention show "% control" activity of ≤ 20% to 1.0 µM in this cell assay. Especially preferred compounds of the present invention show "% control" activity of ≤ 50% to 100 nM in this assay.

[002940] Dopamine beta hydroxylase activity in human plasma was measured by the Nagatsu and Udenfriend method (Nagatsu, T. and Udenfriend, S. "Photometric assay of dopamine-β-hydroxylase activity in human blood." Clin. Chem. 18 (9) 980-983, 1972) with minor modifications. Catalase, N-ethylmaleimide, tyramine, disodium fumarate, pargyline, sodium acetate, ascorbic acid, copper sulfate and octopamine were obtained from Sigma Chemical Co., St. Louis, Mo. 63178. Human plasma samples were obtained from healthy donors (Instituto Português do Sangue Transplantação, Centro Sangue

Transplantation, Porto, Portugal). As of the collection date, the plasma was stored at -80 ° C until use.

The test compounds were initially prepared in dimethyl sulfoxide at a concentration of 10 mM and diluted in dimethyl sulfoxide to the required concentrations.

The test compounds were further diluted in ultrapure water to a concentration 20 times that of the final concentration to be tested.

The final concentrations of test compounds were 10, 100 and 1000 nM.

The various reagents used to prepare the incubation buffer were premixed and consisted of the following components: sodium acetate buffer (1 M, pH 5.0, 18 mL), sodium fumarate (0.2 M, 4.5 mL), ascorbic acid (0.2 M, 4.5 mL, freshly prepared), pargyline (20 mM, freshly prepared, 4.5 mL), N-ethylmaleimide (0.2 M, 4.5 mL) , catalase (10,000 U / mL, 9 mL), copper sulfate (20 µM, 4.5 mL) and ultrapure water 4.5. The standard incubation mix (total volume, 950 µL) contained: 50 µL of compound or carrier (2% dimethyl sulfoxide); 700 µL of incubation buffer; 125 µL of plasma (or saline for the blank reaction or standard curve); 75 µL of saline.

The reaction mixture was placed in a water bath, shaking at 37 ° C and pre-incubated for 10 minutes.

Tyramine (0.5 M) was added and the incubation continued for 45 minutes.

The reaction contents were exposed to air.

A sample of the enzyme preparation (with 125 µL of plasma) to which 2 M perchloric acid was added at the end of the incubation period was used as a blank.

A blank was used for each of the tested compounds.

For the standard octopamine curve, 2 M perchloric acid was replaced by increasing concentrations of octopamine prepared in 2 M perchloric acid (0.5, 1, 2.5, 5, 7.5, 10, 15, 20 µg / mL, final concentration). The incubation was stopped by adding 200 µL of 2 M perchloric acid, and the mixture was centrifuged at 9000 g for 5 min.

The supernatant fluid (800 µL) was transferred to a column (SPE ISOLUTE cartridge

SCX-3, 100 mg) and centrifuged at 150 g for 2 min. The column was washed two more times with 0.5 ml of ultrapure water by centrifugation at 150 g for 2 min. The adsorbed octopamine was eluted twice with 0.3 ml of 4 M ammonium hydroxide by centrifugation at 150 g for 2 min. The octopamine in the eluate was then converted to p-hydroxybenzaldehyde by adding 200 µL of sodium periodate (2%) and incubating for 6 min. The excess periodate was then reduced by adding 200 µL of sodium metabisulfite (10%). Absorbance was measured at 330 mm in a 96-well plate using a SpectraMAX plus 384 spectrophotometer (Molecular Devices) with SOFTmax® PRO Software 5.3 software. The absorbance was linear with the concentration of octopamine from 0.5 to 20 µg / mL. The dopamine beta hydroxylase activity is determined as nmol of octopamine formed / ml of plasma / hour and the effect of the compounds is presented as% control.

[002941] The results are reported in the table below as activity in% control on the tested inhibitor concentration. H. Evaluation of the Pharmacokinetic Profile

[002942] Adult male Wistar rats were kept under controlled environmental conditions (12 h of light / dark cycle, room temperature 22 ± 1 ° C and humidity 50 ± 5%, food and tap water ad libitum). The day before the experiment, the animals were fasted. In experiments designed to assess the pharmacokinetic profile of Examples 56, 66, 199 and 232, rats (n = 4) were administered orally (po) with examples 56, 66, 199 and 232 (10 mg / kg / 4 ml; carrier: 40% kleptose) and plasma and brain samples were collected from anesthetized animals 1 and 2 h after dosing. The animals were anesthetized by intraperitoneal administration of sodium pentobarbital (60 mg / kg). Blood was collected from cardiac puncture into heparinized tubes and kept on ice until centrifugation at 1500 g for 15 min at 4 ° C. Plasma and brain samples were stored at -20 ° C until analysis.

[002943] After thawing, 200 µL of 0.1% formic acid in acetonitrile was added to 100 µL to plasma. The samples were vortexed and centrifuged for 10 min at 10,000 g. The supernatant was filtered and injected on a mass spectrometer.

[002944] After thawing and weighing, water was added to the brain to give a tissue a concentration of 0.1 mg / mL. The samples were then homogenized using a Heidolph DIAX 900 mixer and transferred to plastic tubes. After centrifugation at 10,000 g for 20 min, the supernatant was recovered and treated as described for plasma. I. DβH activity in rat adrenal gland homogenates

[002945] Dopamine beta hydroxylase activity in rat adrenal gland homogenates was measured by the Nagatsu and Udenfriend method (Nagatsu, T. and Udenfriend, S. "Photometric assay of dopamine-β-hydroxylase activity in human blood." Clin Chem 18 (9) 980- 983, 1972) with minor modifications. Catalase, N-ethylmaleimide, tyramine, disodium fumarate, pargyline, sodium acetate, ascorbic acid, copper sulfate and octopamine were obtained from Sigma Chemical Co., St. Louis, Mo. 63178. The test compounds were prepared in 40% kleptose at a concentration of 0.75, 2.5 or 7.5 mg / ml to be administered at a dose of 10 mg / kg. The compounds and carrier (40% kleptose) were administered to wistar rats and the adrenals were collected 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 15 h and 24 h after administration. The samples consisted of the left and right adrenals of each animal. The adrenals were stored in 200 µL of 50 mM Tris pH 7.4 at -30 ° C, starting from the collection date. The samples were homogenized and the homogenates were then quantified for protein.

The protein concentration was adjusted to 1.6 mg / ml.

The various reagents used to constitute the incubation buffer were premixed and consisted of the following components: sodium acetate buffer (1 M, pH 5.0, 6.0 mL), sodium fumarate (0.2 M, 1 , 5 ml), ascorbic acid (0.2 M, 1.5 ml, freshly prepared), pargyline (20 mM, freshly prepared, 1.5 ml), N-ethylmaleimide (0.2 M, 1.5 ml), catalase (55,000 U / ml, 3 ml), copper sulfate (90 µM, 1.67 ml) and ultrapure water (1.33 ml). The standard incubation mix (total volume, 500 µL) contained: 350 µL of incubation buffer; 125 µL of protein sample (or buffer for the blank reaction or standard curve). The reaction mixture was placed in a water bath with agitation at 37 ° C and pre-incubated for 10 minutes.

Tyramine (0.4 M, 25 µL) was added and the incubation continued for 45 minutes.

The reaction contents were exposed to air.

A sample of the enzyme preparation (with 125 µL of protein sample) to which 2 M perchloric acid had been added at the end of the pre-incubation period was used as a blank.

A blank was used for each of the tested compounds.

For the standard octopamine curve, 2 M perchloric acid was replaced by increasing the concentrations of octopamine prepared in 2 M perchloric acid (0.5, 1, 2.5, 5, 7.5, 10 µg / mL, final concentration) . The incubation was stopped by adding 50 µL of 2 M perchloric acid, and the mixture was centrifuged at 16000 g for 3 min.

The supernatant fluid (500 µL) was transferred to a column (SPE ISOLUTE SCX-3 cartridge, 100 mg) and centrifuged at 150 g for 2 min.

The column was washed two more times with 0.5 ml of ultrapure water by centrifuging at 150 g for 2 min.

The adsorbed octopamine was eluted twice with 250 µL of 4 M ammonium hydroxide by centrifuging at 150 g for 2 min.

The octopamine in the eluate was then converted to p-hydroxybenzaldehyde by adding 100 µL of sodium periodate (2%) and incubating for 6 min.

The excess periodate was then reduced by adding 100 µL of sodium metabisulfite (10%). Absorbance was measured at 330 mm in a 96-well plate using a SpectraMAX plus 384 spectrophotometer (Molecular Devices) with SOFTmax® PRO Software 5.3 software. The absorbance was linear with octopamine concentration from 0.5 to 10 µg / mL. The dopamine beta hydroxylase activity is determined as nmol of octopamine formed / mg of protein / hour and the effect of the compounds is presented as% control. J, Catecholamine determination

[002946] The quantification of catecholamines in the brain stem was performed as previously described (Bonifacio, MJ; Sousa, F .; Neves, M .; Palma, N .; Igreja, B .; Pires, NM; Wright, LC; Soares- da- Silva, P. "Characterization of the interaction of the novel anthyhypertensive etamicastat with human dopamine-beta-hydroxylase: comparison with nepicastat." Eur. J. Pharmacol. 751, 50-58, 2015.) with minor modifications. The test compounds were prepared in 40% kleptose at a concentration of 2.5 mg / ml to be administered at a dose of 10 mg / kg. The compounds and transporter (40% kleptosis) were administered to Wistar rats and the tissues (brainstem or left ventricle of the heart) collected in perchloric acid (0.2 M) at defined time points after administration. The tissues were stored overnight at 4 ° C and the solution was then filtered by centrifugation (1500 g, 4 min, 4 ° C) through 0.22 µm pore size filters (Costar Spin-x of Corning Inc., USA). Catecholamines were quantified in filtrates by directly injecting 50 µL of sample volume into an HPLC system with electrochemical detection, using a Spheri-5RP-185 mm column (Perkin-Elmer). The mobile phase consisted of a solution containing 0.1 M citric acid, 0.1 M sodium acetate, 0.15 mM EDTA, 1 mM dibutylamine, 1 mM octyl sulfate, and 5% methanol adjusted to pH 3 , 5 with perchloric acid. K. Biological data Table 1.

[002947] The following table shows the inhibition of DβH in human SKNSH cell line and human plasma for the compounds: Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) ( 0.01 µM) 1 37.9 2 49.3 3 35.8 4 20.3 5 19.9 6 3.7 36.9 7 3.6 45.6 8 15.3 9 54.9 10 2, 1 46.4 11 28.5 12 3.3 30.8 13 13.9 68.0 14 45.6 92.8 15 11.4 66.0 16 12.7 72.9 17 32.2 79.0 18 19.8 81.0 19 16.4 20 2.6 31.0 21 16.7 69.2 22 4.4 45.1 23 8.8 56.6 24 45.6 100.2

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 25 17.6 71.3 26 18.2 64.0 27 7.6 51.6 28 33.8 78.1 29 29.1 72.5 30 73.2 92.0 31 16.7 67.7 32 9.7 46.2 33 33.4 34 0 10.4 35 45, 9 36 50.1 37 15.7 38 20.9 39 29.8 40 29.3 41 60.7 42 8.0 51.5 43 45.6 44 45.9 45 46.8 46 4.3 41, 5 47 62.9 48 48.4 49 33.7 50 1.8 57.5 51 0 0.4 0 5.7 52 0.2 9.2 1.6 10.3 53 0 13.4 2.7 26.2

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 54 4.2 33.8 3.4 32.2 55 3.9 48 , 9 11.1 62.1 56 5.2 45.6 5.5 38.5 57 0.2 11.6 0.1 18.1 58 9.3 56.8 14.0 59.2 59 4, 1 20.8 60 14.0 68.9 61 47.9 99.1 62 10.9 66.4 63 11.9 58.3 64 47.2 88.4 65 12.6 64.5 66 6.4 52.3 67 13.2 76.1 68 13.5 55.6 69 24.1 82.1 70 2.9 36.6 71 11.9 57.0 72 28.9 90.8 73 19.1 75 , 9 74 8.1 70.3 75 56.3 91.0 76 13.1 65.8 77 38.9 87.2 78 24.4 77.3 79 10.3 54.3 80 9.8 60, 7 81 15.9 63.1 82 16.6 69.2

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 83 15.9 78.8 84 1.0 24.5 85 12.2 59.1 86 14.7 70.9 87 13.8 62.8 88 6.1 44.1 89 0 4.3 90 0.4 9.9 91 0 19.0 92 0.1 37.5 93 1 , 0 32.1 94 0.8 47.5 95 0 24.0 96 0.8 22.4 97 0.5 22.7 98 11.7 53.1 99 10.3 55.7 100 2.1 26 , 2 101 3.3 37.2 102 1.7 20.3 103 1.8 21.6 104 19.5 67.9 105 22.0 74.9 106 4.1 33.9 107 6.3 40, 1 108 5.3 46.9 109 1.5 5.4 110 9.7 52.4 111 36.7 89.6

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 112 0 9.9 113 25.6 85.1 114 7.5 58, 4 115 0 48.0 116 68.8 93.8 117 43.0 74.5 118 49.0 89.2 119 87.7 118.2 120 86.2 132.5 121 62.6 79.3 122 13 , 0 70.8 123 6.3 51.9 124 3.3 42.8 125 43.7 106.5 126 40.2 100.2 127 83.8 81.3 128 29.7 98.1 129 10, 3 50.1 130 8.4 55.7 131 50.5 89.8 132 62.3 91.9 133 82.4 95.9 134 3.2 24.9 135 58.1 88.3 136 6.8 44.3 137 21.5 72.9 138 5.0 46.6 139 20.8 77.8 140 26.8 73.1

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 141 76.1 93.2 142 16.2 60.0 143 0.2 20.1 144 0.1 14.7 145 2.0 18.2 146 0.9 13.8 147 2.4 29.0 148 0.9 17.1 149 3.0 52.5 150 17.1 64 , 8 151 20.2 73.7 152 17.8 72.1 153 28.4 85.5 154 38.6 89.5 155 19.7 91.5 156 40.3 88.6 157 24.2 84, 2 158 52.1 90.9 159 50.9 84.3 160 50.8 84.7 161 46.0 85.0 162 31.3 87.2 163 2.4 14.8 164 17.1 65.8 165 14.8 74.3 166 14.1 66.9 167 3.2 28.0 * 50.8 78.0 * 168 10.5 51.9 169 17.1 59.3

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 170 2.0 64.9 171 3.7 40.4 172 8.1 46.3 173 33.1 94.2 174 8.5 52.7 175 13.8 61.7 176 74.9 95.3 177 77.1 99.9 178 29.5 88.2 179 48.8 93 , 5 180 22.3 99.2 181 18.3 68.9 182 71.0 94.6 183 79.8 92.2 184 43.7 89.2 185 30.9 72.9 186 18.0 62, 7 187 21.6 72.6 188 15.4 60.9 189 23.2 87.4 190 19.9 68.6 191 26.0 82.3 192 12.1 73.4 193 46.3 86.0 194 62.4 82.9 195 41.7 77.3 196 68.6 102.2 197 29.4 75.9 198 11.1 99.1 * 52.2 84.5 *

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 199 0.6 84.9 * 27.4 119.3 * 200 66, 4 85.2 201 13.3 62.4 202 22.7 67.7 203 75.8 95.8 204 1.1 26.5 205 18.2 76.9 206 8.7 22.4 207 30.2 76.6 208 13.3 62.0 209 60.3 87.6 210 73.5 94.6 211 94.8 104.9 212 46 86.5 213 66.6 105.9 214 72.1 109.1 215 34.2 74.3 216 47.1 84.5 217 92.3 99.8 218 69.1 89.2 219 19.7 69.9 220 17.7 76.5 221 30.0 79.3 222 12.9 73.6 223 7.2 42.7 224 0.6 22.6 225 12.5 65.3 226 47.4 100.8 227 54.9 86.8

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 228 56.0 90.2 229 38.3 84.3 230 41.6 82.0 231 5.6 35.9 232 6.4 48.8 233 66.8 9.7 * 83.8 59.3 * 234 12.2 43.4 235 1.2 11.4 236 51.0 104.2 237 61.6 92.9 238 88.5 93.4 239 3.9 60.1 240 39.2 76.1 241 8.9 51.7 242 53.6 91.5 243 4.4 37 , 6 * 38.0 87.3 * 244 32.9 83.6 245 93 107.8 246 80.3 115.2 247 35.9 81.7 248 51.8 98.2 249 40.9 96.0 250 7.3 46.1 251 36.0 80.0 252 54.8 6.7 * 82.2 46.0 * 253 24.5 63.4 254 62.2 81.4 255 24.6 71.8 256 29.2 61.7

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 257 92.4 105.9 258 21.3 84.2 259 76.1 90.8 260 26.5 84.1 261 31.8 86.2 262 70.1 82.6 263 87.1 103.3 264 54.2 98.4 265 70.6 94.9 266 56.0 85 , 3 267 55.8 90.8 268 57.7 99.8 269 83.7 105.6 270 53.8 88.1 271 13.2 62.1 272 22.7 73.5 273 28.9 86, 6 274 11.2 55.9 275 24.4 79.0 276 33.3 83.3 277 3.4 35.4 278 62.0 84.2 279 15.7 61.7 280 51.4 92.8 281 29.8 107.9 282 75.4 99.6 283 72.9 96.0 284 41.9 84.8 285 22.2 55.8

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 286 3.4 73.8 287 15.5 66.8 288 81.1 82.0 289 58.3 87.1 290 3.8 37.6 291 1.7 30.2 292 68.3 101.9 293 86.0 104.8 294 1.7 39.7 295 71.5 95 , 6 296 74.5 89.2 297 35.4 78.7 298 28.2 83.5 299 48.4 84.3 300 10.9 57.0 301 6.4 49.1 302 7.7 62, 7 303 34.7 79.3 304 21.1 51.9 305 12.2 61.2 306 18.0 70.6 307 33.0 73.9 308 12.8 64.2 309 38.8 86.2 310 22.3 65.9 311 21.6 87.2 312 51.7 15.0 * 84.8 67.6 * 313 9.6 37.6 314 34.8 1.4 * 80.2 41.9 *

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 315 17.0 53.3 * 67.0 94.0 * 316 4, 5 16.6 * 43.4 73.1 * 317 5.3 45.6 318 61.4 88.4 319 16.5 67.9 320 31.1 90.3 321 13.3 89.7 322 43, 4 62.3 323 43.3 86.3 324 53.1 88.6 325 3.8 34.2 326 59.5 96.6 327 7.0 49.9 328 9.4 63.1 329 16.1 41.7 330 32.5 71.7 331 50.2 77.4 332 2.7 32.8 333 11.7 47.5 334 41.9 80.3 335 8.7 44.9 336 9.4 50 , 0 337 9.4 48.2 338 6.2 36.4 339 4.3 42.3 340 27.0 87.6 341 33.6 91.1 342 16.5 66.6 343 59.5 94, 9

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 344 73.7 88.2 345 40.3 77.2 346 74.9 109.6 347 17.7 79.0 348 44.8 92.4 349 12.5 72.3 350 28.2 85.7 351 16.5 46.2 352 10.9 40.8 353 38.4 90 , 6 354 53.4 106.2 355 14.0 56.4 356 6.6 35.4 357 15.1 62.1 358 24.9 90.1 359 53.3 101.2 360 1.4 22, 5 * 31.8 90.1 * 361 10.4 60.0 362 11.8 43.2 363 20.8 89.5 364 54.7 97.0 365 56.9 101.3 366 81.4 124, 8 367 4.3 45.4 368 63.1 104.4 369 60.1 86.0 370 64.7 88.5 371 17.7 79.0 372 32.0 93.4

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 373 12.8 66.1 374 50.0 97.4 375 40.7 90.0 376 59.3 116.3 377 56.8 102.0 378 52.6 110.2 379 50.1 108.7 380 27.4 74.9 381 3.2 30.0 382 6.0 37 , 6 383 14.8 65.6 384 43.4 104.5 385 19.3 68.1 386 79.4 101.8 387 43.7 92.9 388 71.1 80.8 389 33.1 75, 2 390 52.0 75.0 391 40.7 83.8 392 13.2 62.3 393 65.7 90.6 394 47.6 92.1 395 47.8 96.9 396 10.8 66.9 397 24.1 79.9 398 23.0 94.3 399 4.0 40.6 400 7.3 31.9 401 35.2 66.5

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 402 20.9 59.6 403 4.8 29.9 404 26.2 78.7 405 4.5 50.7 406 2.8 28.9 407 42.3 102.6 408 14.7 77.0 409 64.4 112.6 410 11.1 62.3 411 78.6 104 , 2 412 63.2 106.2 413 3.1 42.4 414 49.0 95.4 415 2.1 14.9 416 25.4 75.3 417 60.5 87.7 418 3.0 27, 7 419 61.0 92.5 420 48.5 87.8 421 5.8 26.1 422 23.2 68.1 423 1.7 18.5 424 20.6 59.5 425 52.0 78.6 426 66.3 83.5 427 34.2 78.1 428 32.3 68.2 429 5.8 37.8 430 2.2 25.3

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 431 10.1 54.3 432 43.7 79.7 433 9.2 56.9 434 8.5 52.5 435 36.6 66.5 436 23.9 73.6 437 6.1 62.7 438 7.5 64.0 439 11.8 67.2 440 8.4 57 , 2 441 37.4 72.8 442 10.0 43.6 443 11.5 59.2 444 57.7 73.5 445 73.7 95.1 446 62.9 83.0 447 33.2 94, 4 448 65.3 93.3 449 2.3 27.8 450 2.3 32.6 451 5.5 39.8 452 12.8 49.6 453 10.4 56.6 454 8.1 56.8 455 50.2 131.0 456 20.2 86.8 457 7.3 42.1 458 12.2 58.5 459 13.5 65.6

Example SKNSH SKNSH Plasma Plasma Plasma (1 µM) (0.1 µM) (1 µM) (0.1 µM) (0.01 µM) 460 18.2 43.9 461 6.9 45.6 462 10.3 50.2 463 3.7 29.1 464 4.5 33.4 465 9.0 62.3 466 6.5 49.6 467 4.0 27.9 468 13.1 65.8 469 1.5 33 , 7 470 79.4 112.0 472 14.2 63.3 473 46.2 98.9 474 79.3 92.5 475 67.0 85.0 476 64.8 94.3 477 59.4 84, 6 478 5.1 46.7 * The compound was tested again under the same experimental conditions. It is believed that the difference between the data generated previously and the data tested again is due to human error. The asterisk data is believed to be correct.

[002948] Table 2.

[002949] The following table shows concentrations in plasma (Cpl) and brain (Cbr) (10 mg / kg, rat, po) for examples 56, 66, 199 and 232: Example Cpl (ng / mL) to Cpl (ng / mL) to Cbr (ng / g) to Cbr (ng / g) at 1h 2h 1h 2h 56 1498 1128 20 21

[002950] As can be seen from the table above, examples 56, 66, 199 and 232 are peripherally selective, i. e., these have significantly higher exposure in plasma compared to the brain. Table 3.

[002951] The following table shows the maximum DβH activity in rat adrenal gland homogenates (ADR) (within 6 h after dose) and norepinephrine (NA) levels in the brainstem (Br.s) (15 h after dose) after oral administration of 10 mg / kg of the compounds of Examples 174, 191, 195, 219, 231, 256 and 403. Each experiment represents mean ± SD of 4 mice. Example DβH activity in NA in Br.s (% ADR (% Control) Control) 174 39 ± 18 84 ± 8 191 45 ± 8 83 ± 10 195 21 ± 9 123 ± 55 219 43 ± 16 92 ± 23 231 43 ± 9 99 ± 14 256 44 ± 22 128 ± 64 403 0 ± 0 87 ± 16

[002952] The table above shows that examples 174, 191, 195, 219, 231, 256 and 403 inhibit DβH at a dose of 10 mg / kg in peripheral tissues, such as ADR. In addition, they failed to reduce NA levels in CNS tissues, such as the brain stem, suggesting that the compounds are peripherally selective.

Claims (17)

1. A compound characterized by the fact that it has formula Ia, or a pharmaceutically acceptable salt or solvate thereof: either D or D or D, where: R1 is hydrogen, C1-C6 alkyl, C1-C6 alkyl partially or totally deuterated or C3-C6 cycloalkyl; R4 is hydrogen or C1-C3 alkyl; R5 is hydrogen; or R4 and R5 combine, together with the carbon atoms to which they are attached, to form a cyclopropyl ring; R6 is -COOH, -CHO, or - (CH2) m-X, where: m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with; X is hydroxy, C1-C3 alkoxy, cyano, -N = CH (NHCN) (NH2), - NH-C (pyrrolidin-1-yl) = NCN, 5- or 6-membered heteroaryl optionally substituted with a methyl, phenyl group , -SO2-R7, - NR8R9, -CO2R10, -CH (CO2R10) 2, -CONR11R12 or -NR13COR14; wherein: R7 is C1-C3 alkyl; R8 is hydrogen or C1-C3 alkyl; R9 is hydrogen, C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl, phenyl, 5 or 6 membered heterocyclyl and 5 or 6 membered heteroaryl substituted with a methyl substituent, C3-C6 cycloalkyl, 5- or 6-membered heteroaryl, or 5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents; or R8 and R9 combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, starch, (N, N-dimethyl) acetamide and pyridyl or with one or two substituents selected from fluoro and oxo, or a 9 or 10 membered heterospirocyclyl group; R10 is hydrogen or C1-C3 alkyl; R11 is hydrogen or C1-C3 alkyl; R12 is hydrogen, C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of cyano, hydroxy, methylsulfonyl, C1-C2 alkoxy, dimethylamino, C3-C6 cycloalkyl, phenyl, heteroaryl with 5 or 6 members optionally substituted with a methyl and heterocyclyl substituent with 5 or 6 members optionally substituted with a t-Boc group or with one or two fluoro substituents, C3-C6 cycloalkyl optionally substituted with a substituent selected from the group consisting of cyano, hydroxy, hydroxymethyl and oxo, cyan, methylsulfonyl, CH2COO (C1-C3 alkyl), 5- or 6-membered heteroaryl optionally substituted with a methyl substituent, 4-, 5 or 6-membered heterocyclyl optionally substituted with one or two selected oxo and methyl substituents, CH2CH (NH2) (COOH ), or CH (CH3) CONH2; or R11 and R12 combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from monofluromethyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, cyano, starch, (N, N-dimethyl) acetamide and pyridyl, or with one or two substituents selected from fluoro, methyl and oxo, or optionally fused with a cyclopropyl ring which can be substituted with one or two methyl substituents, or a group heterospirocyclyl with 9 or 10 members; R13 is hydrogen or C1-C3 alkyl; R14 is C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl and phenyl, C3-C6 cycloalkyl, 5 or 6-membered heteroaryl, or 5-membered heterocyclyl or 6 members optionally substituted with one or two oxo substituents; A is C5-C7 cycloalkyl, furanyl, thiophenyl, methylthiophenyl or X1 X1 'X2 X2' X3, where: X1 is hydrogen, halo or methyl; X1 'is hydrogen or halo; X2 is hydrogen, halo or methyl; X2 'is hydrogen or halo; X3 is hydrogen or fluoro; n is 0 or 1, and when n is 0 a single bond is attached to the carbon atoms to which the CH2 moiety would be attached when n is 1 for use in therapy. 2. A compound characterized by the fact that it has formula Ia, or a pharmaceutically acceptable salt or solvate thereof: either D or D or D, where: R1 is hydrogen, C1-C6 alkyl, C1-C6 alkyl partially or totally deuterated or C3-C6 cycloalkyl; R4 is hydrogen or C1-C3 alkyl; R5 is hydrogen; or R4 and R5 combine, together with the carbon atoms to which they are attached, to form a cyclopropyl ring; R6 is -COOH, -CHO, or - (CH2) m-X, where: m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with; X is hydroxy, C1-C3 alkoxy, cyano, -N = CH (NHCN) (NH2), -NH- C (pyrrolidin-1-yl) = NCN, 5- or 6-membered heteroaryl optionally substituted with a methyl, phenyl group , -SO2-R7, -NR8R9, -CO2R10, - CH (CO2R10) 2, -CONR11R12 or -NR13COR14; wherein: R7 is C1-C3 alkyl; R8 is hydrogen or C1-C3 alkyl; R9 is hydrogen, C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl, phenyl, 5 or 6 membered heterocyclyl and 5 or 6 membered heteroaryl substituted with a methyl substituent, C3-C6 cycloalkyl, 5- or 6-membered heteroaryl, or 5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents; or R8 and R9 combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, starch, (N, N-dimethyl) acetamide and pyridyl or with one or two substituents selected from fluoro and oxo, or a 9 or 10-membered heterospirocyclic group; R10 is hydrogen or C1-C3 alkyl; R11 is hydrogen or C1-C3 alkyl; R12 is hydrogen, C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of cyano, hydroxy, methylsulfonyl, C1-C2 alkoxy, dimethylamino, C3-C6 cycloalkyl, phenyl, heteroaryl with 5 or 6 members optionally substituted with a methyl and heterocyclyl substituent with 5 or 6 members optionally substituted with a t-Boc group or with one or two fluoro substituents, C3-C6 cycloalkyl optionally substituted with a substituent selected from the group consisting of cyano, hydroxy, hydroxymethyl and oxo, cyano, methylsulfonyl, CH2COO (C1-C3 alkyl), 5 or 6 membered heteroaryl optionally substituted with a methyl substituent, 4, 5 or 6 membered heterocyclyl optionally substituted with one or two selected oxo and methyl substituents, CH2CH (NH2) (COOH), or CH (CH3) CONH2; or R11 and R12 combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with a substituent selected from monofluromethyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, cyano, starch, (N, N-dimethyl) acetamide and pyridyl, or with one or two substituents selected from fluoro, methyl and oxo, or optionally fused with a cyclopropyl ring which can be substituted with one or two methyl substituents, or a group heterospirocyclyl with 9 or 10 members; R13 is hydrogen or C1-C3 alkyl; R14 is C1-C4 alkyl optionally substituted with up to three fluoro substituents or with a substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl and phenyl, C3-C6 cycloalkyl, 5 or 6-membered heteroaryl, or 5-membered heterocyclyl or 6 members optionally substituted with one or two oxo substituents; A is C5-C7 cycloalkyl, furanyl, thiophenyl, methylthiophenyl or X1 X1 'X2 X2' X3, where: X1 is hydrogen, halo or methyl; X1 'is hydrogen or halo; X2 is hydrogen, halo or methyl; X2 'is hydrogen or halo; X3 is hydrogen or fluoro; n is 0 or 1, and when n is 0 a single bond is attached to the carbon atoms to which the CH2 unit would be attached when n is 1. A compound for use in therapy according to claim 1, or a compound according to claim 2, characterized by the fact that n is 0. A compound for use in therapy according to claim 1 or 3, or a compound according to claim 2 or 3, characterized in that R4 and R5 combine together with the carbon atom to which they are attached to form a cyclopropyl ring. Compound for use in therapy according to claims 1 or 3 to 4, or a compound according to claims 2 to 4, characterized in that more than 50% of the substituents R5 and A have the stereochemical configuration of formula Id or D or D or D A compound for use in therapy according to claims 1 or 3 to 4, or a compound according to claims 2 to 4, characterized in that more than 50% of the substituents R5 and A have the stereochemical formula configuration Ie or D or D or D A compound for use in therapy according to claims 1 or 3 to 6, or a compound according to claims 2 to 6, characterized in that A is X1 X1 'X2 X2' X3, wherein X1, X1 ', X2, X2' and X3 are as defined in claim 1. A compound for use in therapy according to claims 1 or 3 to 7, or a compound according to claims 2 to 7, characterized in that R1 is hydrogen, methyl or d3-methyl. Compound for use in therapy according to claims 1, 3 or 5 to 8, or a compound according to claims 2, 3 or 5 to 8, characterized in that R4 is hydrogen or methyl. A compound for use in therapy according to claims 1, 3 or 5 to 9, or a compound according to claims 2, 3 or 5 to 9, wherein R5 is hydrogen. A compound for use in therapy according to claims 1 or 3 to 10, or a compound according to claims 2 to 10, characterized in that R6 is -COOH, - CHO, or - (CH2) mX, where: m is 1, 2 or 3 and a -CH2- unit within - (CH2) m- can optionally be replaced with; X is hydroxy, ethoxy, cyano, -N = C (NHCN) (NH2), -NH-C (pyrrolidin-1-yl) = NCN, 1-methylimidazol-2-yl, 3-methyl-1,2,4 -oxadiazole-5-yl, tetrazole-5- ila, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl, -SO2-R7, -NR8R9, -COOR10, -CH (COOR10) 2, -CONR11R12 or -NR13COR14; where: R7 is methyl; R8 is hydrogen or methyl; R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3-yl, (tetrahydrofuran-2-yl) methyl, (1,1-dioxide) tetrahydrothiopyran-4-yl, (tetrahydro-2H-pyran-4-yl) methyl, pyridin-2-yl, pyridin-3 -yl, tetrahydropyran-3-yl, cyclohexyl, (pyridin-2-yl) methyl or (1-methylpyrazol-4-yl) methyl; or R8 and R9 combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group; R10 is hydrogen, methyl or ethyl; R11 is hydrogen or methyl; R12 is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl) methyl, (pyridin-3-yl) methyl, (Nt-Boc-pyrrolidin-2-yl) methyl, 2-hydroxyethyl, 2-methoxyethyl , 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, 2- (pyridin-2-yl) ethyl, 2- (1H-pyrazol-1-yl) ethyl, 2- (4,4- difluoropiperidin-1-yl) ethyl, propyl, isopropyl, 3- (N, N-dimethylamino) propyl, 3- (morpholin-1-yl) propyl, butyl, cyclopropyl, 1- cyanocyclopropyl, cyclobutyl, cyclopentyl, 2-hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH2COOEt, tetrahydrofuran-3-yl, 2-oxotetrahydrofuran-3-yl, tetra- hydropyran-3-yl, tetrahydropyran-4-yl, (1,1-dioxide) tetrahydrothiopyran-4-yl, 1,3,4- thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH2CH (NH2) (COOH), CH (CH3) CONH2, oxazol-2-yl, (pyrazine-2-yl) methyl, oxetan-3 -yl, (tetrahydrofuran-2-yl) methyl, (1-methylpyrazol-4-yl) methyl, thiazol-2-yl, 2-oxopyrrolidin-3-yl, 2-cyanocyclopentyl, isoxazol-4-yl, 3 -methyl-1,2,4-oxadiazol-5-yl, (tetrahydropyran-4-yl) methyl, 2-oxopiperidin-3-yl, 1-methylpyrazol-4-yl, isothiazol-4-yl, 1- methyl-2-oxopiperidin-5-yl, 1-methyl-2-oxopyrrolidin-3-yl, 1-methyl-5-oxopyrrolidin-3-yl or 1-methyl-2-oxopyrrolidin-4-yl; or R11 and R12 combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3- (fluoromethyl) pyrrolidinyl group, 3-methylsulfonyl-pyrrolidinyl, N, N-dimethylpyrrolidinyl-3-carboxamide, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl, 4-hydroxymethyl-piperidinyl, 4-amido-piperidinyl, 4 methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N, N-dimethylpiperidinyl-4-carboxamide, N4-methyl-piperazinyl, N4- (N, N-dimethyl) acetamide-piperazinyl, N4- (pyridine-2-yl) piperazinyl, morpholinyl, thiomorpholinyl, 1-oxothiomorpholinyl, 1,1-dioxidothiomorpholinyl, 2-oxa-7- azaespiro [4.4] nonanila, 2-oxa-8-azaespiro [4.5] decanil, 1,4-dioxa-8-azaespiro [ 4.5] decanyl, 6,6-dimethyl-3-azabicyclo [3.1.0] hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3-oxopiperazinyl, 2-cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3-fluoromethylpyrrolidinyl or 3- (N , N-dimethylacetamide) pyrrolidinyl; R13 is hydrogen or methyl; R14 is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl. Compound for use in therapy according to claims 1 or 3 to 11, or a compound according to claims 2 to 11, characterized by the fact that it has A is X1 X1 'X2 X2' X3, where: X1 is hydrogen, fluoro, chloro or methyl; X1 'is hydrogen, fluoro or chloro; X2 is hydrogen, fluoro, chloro, bromo or methyl; X2 'is hydrogen, fluoro, chloro or bromo; X3 is hydrogen or fluoro. A compound of formula Ia, as defined in any one of claims 2 to 12, or a pharmaceutically acceptable salt or solvate thereof, characterized in that it is for use in the treatment of conditions eased by inhibition of dopamine beta-hydroxylase outside the central nervous system. Use of a compound of formula Ia, as defined in any of claims 2 to 12, or a pharmaceutically acceptable salt or solvate thereof, characterized in that it is for the manufacture of a medicament for the treatment of conditions eased by inhibition of dopamine-beta-hydroxylase outside the central nervous system. 15. Method for treating or preventing conditions eased by dopamine beta-hydroxylase inhibition outside the central nervous system characterized by the fact that it comprises administering a therapeutically effective amount of a compound of formula Ia, as defined in any of claims 2 to 12 , or a pharmaceutically acceptable salt or solvate thereof, to a patient in need. 16. Pharmaceutical composition characterized by the fact that it comprises (i) a therapeutically effective amount of a compound of formula Ia, as defined in any one of claims 2 to 12, or a pharmaceutically acceptable salt or solvate thereof; and (ii) a pharmaceutically acceptable excipient. A compound of formula Ia, as defined in any one of claims 2 to 5 or 7 to 12, or a pharmaceutically acceptable salt or solvate thereof, characterized in that it has the proviso that the compound (S) -1-benzyl -6- (3,5-difluorophenyl) -6,7-dihydro-2H-pyrrolo [1,2-c] imidazole-3 (5H) -thione is excluded.